ArticlePLoS pathogens2009
Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 145 citations in OpenAlex.
- A detailed characterization of drug resistance during darunavir/ritonavir monotherapy highlights a high barrier to the emergence of resistance mutations in protease but identifies alternative pathways of resistance.The Journal of antimicrobial chemotherapy · 2024Trial
- Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy.Antimicrobial agents and chemotherapy · 2016Trial
- Trial
- Gag mutations can impact virological response to dual-boosted protease inhibitor combinations in antiretroviral-naïve HIV-infected patients.Antimicrobial agents and chemotherapy · 2010Trial
- Antiretroviral medication adherence and class- specific resistance in a large prospective clinical trial.AIDS (London, England) · 2010Trial
- Subtype-Specific HIV-1 Protease and the Role of Hinge and Flap Dynamics in Drug Resistance: A Subtype C Narrative.Viruses · 2025Review
- Consensus Sequences forViruses · 2025Article
- Noncanonical HIV drug resistance mutations: need to close existing gaps.AIDS (London, England) · 2025Review
- Development of HIV Drug-Resistance Mutations and Antiretroviral Efficacy Among Vietnamese Patients After Failure of 5-Year First-Line Therapy.Journal of clinical laboratory analysis · 2025Observational
- Comparative Evaluation of Open-Source Bioinformatics Pipelines for Full-Length Viral Genome Assembly.Viruses · 2024Article
- HIV-1 envelope facilitates the development of protease inhibitor resistance through acquiring mutations associated with viral entry and immune escape.Frontiers in microbiology · 2024Article
- Evolving Mutational Buildup in HIV-1 Protease Shifts Conformational Dynamics to Gain Drug Resistance.Journal of chemical information and modeling · 2023Article
- Comprehending the Structure, Dynamics, and Mechanism of Action of Drug-Resistant HIV Protease.ACS omega · 2023Review
- Article
- Antiretroviral Drug-Resistance Mutations on thePathogens (Basel, Switzerland) · 2022Article
- Covariation of viral recombination with single nucleotide variants during virus evolution revealed by CoVaMa.Nucleic acids research · 2022Article
- Detection of Gag C-terminal mutations among HIV-1 non-B subtypes in a subset of Cameroonian patients.Scientific reports · 2022Article
- Genetic Diversity and Low Therapeutic Impact of Variant-Specific Markers in HIV-1 Pol Proteins.Frontiers in microbiology · 2022Article
- Absence of Lenacapavir (GS-6207) Phenotypic Resistance in HIV Gag Cleavage Site Mutants and in Isolates with Resistance to Existing Drug Classes.Antimicrobial agents and chemotherapy · 2021Article
- Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus type 1 (HIV-1) resistance to protease inhibitors (PI) results from mutations in the viral protease (PR) that reduce PI binding but also decrease viral replicative capacity (RC). Additional mutations compensating for the RC loss subsequently accumulate within PR and in Gag substrate cleavage sites. We examined the respective contribution of mutations in PR and Gag to PI resistance and RC and their interdependence using a panel of HIV-1 molecular clones carrying different sequences from six patients who had failed multiple lines of treatment. Mutations in Gag strongly and directly contributed to PI resistance besides compensating for fitness loss. This effect was essentially carried by the C-terminal region of Gag (containing NC-SP2-p6) with little or no contribution from MA, CA, and SP1. The effect of Gag on resistance depended on the presence of cleavage site mutations A431V or I437V in NC-SP2-p6 and correlated with processing of the NC/SP2 cleavage site. By contrast, reverting the A431V or I437V mutation in these highly evolved sequences had little effect on RC. Mutations in the NC-SP2-p6 region of Gag can be dually selected as compensatory and as direct PI resistance mutations, with cleavage at the NC-SP2 site behaving as a rate-limiting step in PI resistance. Further compensatory mutations render viral RC independent of the A431V or I437V mutations while their effect on resistance persists.
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