Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates.
PMID: 20956600
2011
Antimicrobial agents and chemotherapy
Abstract: Although samples with the Y143R/C mutation had reduced susceptibility to RAL, they remained susceptible to MK-2048 and compound G.
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
PMID: 21576445
2011
Antimicrobial agents and chemotherapy
Abstract:
Abstract: Assays without RAL suggested that the T97A mutation could rescue the catalytic activity which was impaired by the presence of the Y143C/R mutation.
Abstract: FCs of 18 and 100 were observed with the strand transfer assay for IN Y143C/T97A and Y143R/T97A mutations, with IC(50) of 0.625 muM and 2.5 muM, respectively.
Abstract: In the strand transfer assay, the IN Y143C or R mutation combined with the secondary mutation T97A severely impaired susceptibility to RAL compared to results with the IN Y143C or R mutation alone.
Switching between raltegravir resistance pathways analyzed by deep sequencing.
Introduction: Three codons can mutate to generate primary resistance mutations, which encode Y143R/C/H, Q148H
Discussion: Our findings taken together support the idea that Y143H, and possibly Y143C and Q148R, are authentic replication-competent polymorphisms that are present in viral populations in the absence of RAL.
Discussion: The Y143C and Q148R substitutions were marginally significant by some measures but did not survive correction for multiple comparisons.
Discussion: also investigated RAL resistance using 454 sequencing and reported detection of Y143H, Y143C, and Q148R prior to initiation of therapy.
Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal.
Abstract: RESULTS: At the time of RAL withdrawal, virus exhibited different integrase resistance pathways: G140S/Q148R, E92Q/N155H, T97A/N155H and T97A/Y143C.
Abstract: Regarding patient 4, the mutant T97A/Y143C was still detected at M1 and M3 following RAL withdrawal.
Drug Susceptibility and Viral Fitness of HIV-1 with Integrase Strand Transfer Inhibitor Resistance Substitution Q148R or N155H in Combination with Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Resistance Substitutions.
Abstract: Amino acid changes Q148R and N155H individually conferred resistance to raltegravir (14-fold and seven-fold, respectively), whereas the Y143C replacement had no statistically significant effect on raltegravir sensitivity.
Introduction: Specific amino acid changes that are known to confer raltegravir resistance in HIV-1 have been observed in integrase sequences from raltegravir-treated HIV-2 patients; these commonly include
Introduction: recently reported that Q148R and N155H individually improve the ability of purified HIV-2 integrase to catalyze strand transfer in the presence of raltegravir, whereas the Y143C change alone had no impact on raltegravir sensitivity.
Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance.
Discussion: Additional, head-to-head comparisons of the phenotypic effects of Y143C in HIV-1 and HIV-2 are needed to resolve this issue.
Discussion: Cooperative effects were also observed between the E92Q and Y143C replacements in HIV-2 integrase; although these changes individually had no measurable effect on raltegravir sensitivity, the E92Q with Y143C enzyme was approximately 10-fold resistant to the inhibitor.
Discussion: In contrast, the Y143C replacement in HIV-2 integrase had little or no effect on raltegravir sensitivity.
Discussion: found that Y143C conferred 16-fold resistance to raltegravir in the Phenosense HIV-1 single-cycle test.
Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis.
Result: reported the formation of S-S bond between Y143C and position 2 next to 5'-end of the non-processed viral DNA.
Natural polymorphisms of integrase among HIV type 1-infected South African patients.
PMID: 20377427
2010
AIDS research and human retroviruses
Abstract: Amino acid sequence analysis revealed there were no primary mutations (Y143R/C/H, Q148H/R/K, and N155H/S) associated with reduced susceptibility to the integrase inhibitors raltegravir and elvitegravir.
The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not viral fitness of primary virus isolates.
Abstract: OBJECTIVE: : Resistance to raltegravir is associated with three genetic pathways defined by the mutations Y143R/C, Q148H/R/K or N155H in integrase, which also infer a viral fitness cost.
Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo.
PMID: 19901095
2010
Antimicrobial agents and chemotherapy
Abstract: A molecular modeling study confirmed that Y143R/C mutations play a role similar to that determined for Q148R/H mutations.
Abstract: Furthermore, the 50% effective concentration (EC(50)) determined for Y143R/C mutants was significantly higher than that obtained with G140S/Q148R mutants.
Abstract: However, Y143R/C activity can be kinetically restored, thereby reproducing the effect of the secondary G140S mutation that rescues the defect associated with the Q148R/H mutants.
Abstract: Our observations demonstrate that Y143R/C mutants are strongly impaired for both of these activities in vitro.
HIV mutation literature information.
PMID: 
2011
Antimicrobial agents and chemotherapy
Browser Board
Co-occurred Entities
Filtrator
ViMRT