ArticleProceedings of the National Academy of Sciences of the United States of America2009
Resistance to CCR5 inhibitors caused by sequence changes in the fusion peptide of HIV-1 gp41.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- Evolution of Multiple Domains of the HIV-1 Envelope Glycoprotein during Coreceptor Switch with CCR5 Antagonist Therapy.Microbiology spectrum · 2022Trial
- HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug.Journal of virology · 2012Trial
- Mutations in S2 subunit of SARS-CoV-2 Omicron spike strongly influence its conformation, fusogenicity, and neutralization sensitivity.Journal of virology · 2023Article
- Modeling of CCR5 Recognition by HIV-1 gp120: How the Viral Protein Exploits the Conformational Plasticity of the Coreceptor.Viruses · 2021Article
- Dopamine Levels Induced by Substance Abuse Alter Efficacy of Maraviroc and Expression of CCR5 Conformations on Myeloid Cells: Implications for NeuroHIV.Frontiers in immunology · 2021Article
- CCR5 structural plasticity shapes HIV-1 phenotypic properties.PLoS pathogens · 2018Article
- Article
- Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike.Nature · 2017Article
- Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5.Pharmacology research & perspectives · 2016Article
- CCR5 receptor antagonists in preclinical to phase II clinical development for treatment of HIV.Expert opinion on investigational drugs · 2016Review
- Frequency and Env determinants of HIV-1 subtype C strains from antiretroviral therapy-naive subjects that display incomplete inhibition by maraviroc.Retrovirology · 2016Article
- Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors.Retrovirology · 2016Article
- Reduced Baseline Sensitivity to Maraviroc Inhibition Among R5 HIV-1 Isolates From Individuals With Severe Immunodeficiency.Journal of acquired immune deficiency syndromes (1999) · 2016Article
- Development of Small-molecule HIV Entry Inhibitors Specifically Targeting gp120 or gp41.Current topics in medicinal chemistry · 2016Review
- Characterizing the Diverse Mutational Pathways Associated with R5-Tropic Maraviroc Resistance: HIV-1 That Uses the Drug-Bound CCR5 Coreceptor.Journal of virology · 2015Article
- A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity.Retrovirology · 2015Article
- Pairwise growth competition assay for determining the replication fitness of human immunodeficiency viruses.Journal of visualized experiments : JoVE · 2015Article
- Review
- V3-independent competitive resistance of a dual-X4 HIV-1 to the CXCR4 inhibitor AMD3100.PloS one · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
We have investigated the mechanism of resistance of a HIV type 1 (HIV-1) R5 primary isolate, D1/85.16, to the small molecule CCR5 inhibitor, vicriviroc (VVC). Unlike other viruses resistant to this class of compound, D1/85.16 lacks sequence changes in the V3 region of the gp120 surface glycoprotein. Inspection of env sequences from D1/85.16 compared with those derived from the parental, inhibitor-sensitive virus, CC1/85, revealed a cluster of 3 conservative changes in the fusion peptide (FP) of the gp41 transmembrane glycoprotein that tracked with the resistance phenotype. Studies with engineered Env-chimeric and point-substituted viruses confirmed that these 3 FP residues were substantially responsible for VVC resistance without altering coreceptor usage, as assessed in both peripheral blood mononuclear cells and the TZM-bl cell line. VVC resistance is manifested differently in the 2 cell types, and there are assay-dependent complexities to the dose-response curves for the engineered resistant viruses. To explain them, we created a model for resistance and generated theoretical VVC inhibition curves that closely mimic the experimental data for the resistant viruses. The basis for the model is the existence of distinct forms of CCR5, with varying affinities for small molecule CCR5 inhibitors that are presumed to be present in different proportions on different cell types, and are used selectively by resistant HIV-1 variants when ligated with an inhibitor. Together, the experimental results and theoretical model may help understand how HIV-1 uses CCR5 to enter target cells under various conditions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.