Abstract: Major integrase mutations included T66AIK, E92QV, F121Y, Y143CHR, S147G, Q148HKR, and N155H; multiple accessory mutations were also assessed.
HIV-1-infected patients with advanced disease failing a raltegravir-containing salvage regimen in Sao Paulo, Brazil.
PMID: 24359837
2014
International journal of antimicrobial agents
Abstract: At failure, major RAL resistance mutations included Q148H/R/K (21/47; 45%), N155H (14/47; 30%), Y143R/H/C (3/47; 6%) and E92Q (1/47; 2%).
Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants.
PMID: 24471816
2014
Journal of medicinal chemistry
Abstract: Importantly, some of these new inhibitors retain greater antiviral efficacy compared to that of RAL when tested against a panel of IN mutants that included Y143R, N155H, G140S/Q148H, G118R, and E138K/Q148K.
Method: The following sense with cognate antisense (not shown) oligonucleotides (Integrated DNA Technologies, Coralville, IA) was used in the mutagenesis: G118R, 5'-GTACATACAGACAATCGCAGCAATTTCACCAGTAC-3'; E138K, 5'-GGCGGGGATCAAGCAGAAATTTGGCATTCCCTA-3'; G140A, 5'-GGGGATCAAGCAGGAATTTGCCATTCCCTACAATC-3'; G140S, 5'-GGGGATCAAGCAGGAATTTAGCATTCCCTACAATC-3';
Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy.
Method: Patients with more than one darunavir resistance-associated mutation or with known major integrase resistance-associated mutations (N155H, Q148H/R/K, Y143C/R, and G140S) were excluded from the study.
Effect of HIV-1 integrase resistance mutations when introduced into SIVmac239 on susceptibility to integrase strand transfer inhibitors.
Abstract: Each of the G118R, Y143R, Q148R, R263K, and G140S/Q148R mutations, when introduced into SIV, impaired infectiousness and replication fitness compared to wild-type virus.
Abstract: In contrast, Y143R, Q148R, and N155H all yielded low levels of resistance to RAL.
2014 Update of the drug resistance mutations in HIV-1.
Discussion: Raltegravir failure is associated with integrase mutations in at least 3 distinct, but not exclusive, genetic pathways defined by 2 or more mutations including (1) a signature (major) mutation at Q148H/K/R, N155H, or Y143R/H/C; and (2) 1 or more additional minor mutations.
Discussion: The Y143R/H/C mutation is uncommon.
Activities, crystal structures, and molecular dynamics of dihydro-1H-isoindole derivatives, inhibitors of HIV-1 integrase.
Result: As expected, the Y143R mutation had minimal impact on the activity of our five derivatives (less than 2.5-fold) whereas it induced a loss of sensitivity to RAL (37-fold increase in IC50) (Figure 1B).
Result: Because the Y143R mutant has only minimal effect on the activity of XZ-259, it seems that the additional interactions enabled with the dimethyl sulfonamide are conserved in this arginine mutant.
Result: Consequently, XZ-259 is over 10-time more potent than RAL at inhibiting the Y143R mutant virus.
Result: Consistent with our biochemical assays, the Y143R mutation had minimal effect on the antiviral potency of our dihydro-1H-isoindole series (including XZ-259) with less than 2-fold increase in EC50 values.
Result: However, both conformations predicted modest (2- to 8-fold) increases in IC50 against the PMID: 23733474
2013
Antimicrobial agents and chemotherapy
Abstract:
Abstract: Here we describe clinical isolates with alternative substitutions at position 143 (Y143A, Y143G, Y143H, and Y143S [Y143A,G,H,S]) that emerge less frequently, and we compare the genotypic and phenotypic profiles of these viruses to Y143C,R viruses to reconcile the preferential selection of Y143C,R variants during RAL treatment.
Abstract: Our observations demonstrate that the RAL resistance profiles of Y143A,G,H,S viruses and their association with specific secondary substitutions are similar to the well-established Y143C profile but distinct from the Y143R profile.
Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza as integrase inhibitor.
Discussion: In the WT structure, the side chain of Tyr143 was found to form a direct pi-pi stacking interaction with oxadiazole ring of raltegravir, however, the replacement of Tyr by Arg (Y143R) disturbs this type of interaction, thereby could possible significantly influence drug inhibitory potency .
Discussion: The hypothetically predicted mode of action of these two compounds against the Y212R (corresponding to Y143R HIV-1 IN) and N224H (corresponding to N155H HIV-1 IN) PFV IN are displayed in (Figures 3B & 3C), respectively.
Discussion: The proposed raltegravir resistance pathway of the less frequently PMID: 23798668
2013
The Journal of antimicrobial chemotherapy
Abstract: No variations were observed for the Y143R/C (+/-T97A) or N155H variants.
Abstract: RESULTS: Y143R single mutants conferred a higher level of raltegravir resistance in macrophages [fold change (FC) 47.7-60.24] compared with CD4+ T cells (FC 9.55-11.56).
Abstract: When compared with raltegravir, none to modest increases in resistance were observed for the Y143R/C pathways.
HIV mutation literature information.
PMID: 
2014
Clinical infectious diseases
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