ArticleJournal of virology2000
Retracing the evolutionary pathways of human immunodeficiency virus type 1 resistance to protease inhibitors: virus fitness in the absence and in the presence of drug.
Article in Journal of virology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 186 citations in OpenAlex.
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- An oral non-covalent non-peptidic inhibitor of SARS-CoV-2 Mpro ameliorates viral replication and pathogenesis in vivo.Cell reports · 2024Article
- Mechanistic causes of sign epistasis and its applications.Frontiers in genetics · 2024Review
- Antiretroviral therapy resistance mutations among HIV infected people in Kazakhstan.Scientific reports · 2022Article
- Sequence dependencies and biophysical features both govern cleavage of diverse cut-sites by HIV protease.Protein science : a publication of the Protein Society · 2022Article
- Target-Based Design of Promysalin Analogues Identifies a New Putative Binding Cleft in Succinate Dehydrogenase.ACS infectious diseases · 2020Article
- Purifying Selection in Human Immunodeficiency Virus-1Journal of clinical medicine research · 2020Article
- Natural selection favoring more transmissible HIV detected in United States molecular transmission network.Nature communications · 2019Article
- Antiretroviral resistance in HIV-1 patients at a tertiary medical institute in Saudi Arabia: a retrospective study and analysis.BMC infectious diseases · 2018Article
- Neutral Theory and Rapidly Evolving Viral Pathogens.Molecular biology and evolution · 2018Article
- Transmission fitness of drug-resistant HIV revealed in a surveillance system transmission network.Virus evolution · 2017Article
- CIB1 and CIB2 are HIV-1 helper factors involved in viral entry.Scientific reports · 2016Article
- Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein.PLoS genetics · 2016Article
- HIV-1 subtypes and drug resistance profiles in a cohort of heterosexual patients in Istanbul, Turkey.Medical microbiology and immunology · 2015Article
- Estimating HIV-1 fitness characteristics from cross-sectional genotype data.PLoS computational biology · 2014Article
- Contribution of silent mutations to thermal adaptation of RNA bacteriophage Qβ.Journal of virology · 2014Article
- A sensitive real-time PCR based assay to estimate the impact of amino acid substitutions on the competitive replication fitness of human immunodeficiency virus type 1 in cell culture.Journal of virological methods · 2013Article
- The choreography of HIV-1 proteolytic processing and virion assembly.The Journal of biological chemistry · 2012Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus type 1 (HIV-1) resistance to protease inhibitors (PI) is a major obstacle to the full success of combined antiretroviral therapy. High-level resistance to these compounds is the consequence of stepwise accumulation of amino acid substitutions in the HIV-1 protease (PR), following pathways that usually differ from one inhibitor to another. The selective advantage conferred by resistance mutations may depend upon several parameters: the impact of the mutation on virus infectivity in the presence or absence of drug, the nature of the drug, and its local concentration. Because drug concentrations in vivo are subject to extensive variation over time and display a markedly uneven tissue distribution, the parameters of selection for HIV-1 resistance to PI in treated patients are complex and poorly understood. In this study, we have reconstructed a large series of HIV-1 mutants that carry single or combined mutations in the PR, retracing the accumulation pathways observed in ritonavir-, indinavir-, and saquinavir-treated patients. We have then measured the phenotypic resistance and the drug-free infectivity of these mutant viruses. A deeper insight into the evolutionary value of HIV-1 PR mutants came from a novel assay system designed to measure the replicative advantage of mutant viruses as a function of drug concentration. By tracing the resultant fitness profiles, we determined the range of drug concentrations for which mutant viruses displayed a replicative advantage over the wild type and the extent of this advantage. Fitness profiles were fully consistent with the order of accumulation of resistance mutations observed in treated patients and further emphasise the key importance of local drug concentration in the patterns of selection of drug-resistant HIV-1 mutants.
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