ArticleJournal of virology2010
A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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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
66 citing papers in PubMed.
- Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species.PLoS pathogens · 2022Trial
- Genotypic analysis of the V3 region of HIV from virologic nonresponders to maraviroc-containing regimens reveals distinct patterns of failure.Antimicrobial agents and chemotherapy · 2013Trial
- Vicriviroc resistance decay and relative replicative fitness in HIV-1 clinical isolates under sequential drug selection pressures.Journal of virology · 2012Trial
- Review
- Downregulation of CCR5 on brain perivascular macrophages in simian immunodeficiency virus-infected rhesus macaques.Brain and behavior · 2023Article
- Opening the door on entry inhibitors in HIV: Redefining the use of entry inhibitors in heavily treatment experienced and treatment-limited individuals living with HIV.HIV medicine · 2022Review
- Enhancement of CD4 Binding, Host Cell Entry, and Sensitivity to CD4bs Antibody Inhibition Conferred by a Natural but Rare Polymorphism in the HIV-1 Envelope.Journal of virology · 2022Article
- Article
- Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages.Virulence · 2020Review
- Specific Substitutions in Region V2 of gp120Pathogens (Basel, Switzerland) · 2020Article
- Extra-Low-Frequency Pulse Stimulated Conformational Change in Blood-Cell Proteins and Consequent Immune Activity Transformation.IEEE journal of translational engineering in health and medicine · 2020Article
- Targeting CCR5 trafficking to inhibit HIV-1 infection.Science advances · 2019Article
- Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.Journal of virology · 2018Article
- Adding an Artificial Tail-Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile.Molecules (Basel, Switzerland) · 2017Article
- Article
- Article
- The Membrane-Proximal Region of C-C Chemokine Receptor Type 5 Participates in the Infection of HIV-1.Frontiers in immunology · 2017Article
- Driving HIV-1 into a Vulnerable Corner by Taking Advantage of Viral Adaptation and Evolution.Frontiers in microbiology · 2017Review
- 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
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
CCR5 antagonists inhibit HIV entry by binding to a coreceptor and inducing changes in the extracellular loops (ECLs) of CCR5. In this study, we analyzed viruses from 11 treatment-experienced patients who experienced virologic failure on treatment regimens containing the CCR5 antagonist maraviroc (MVC). Viruses from one patient developed high-level resistance to MVC during the course of treatment. Although resistance to one CCR5 antagonist is often associated with broad cross-resistance to other agents, these viruses remained sensitive to most other CCR5 antagonists, including vicriviroc and aplaviroc. MVC resistance was dependent upon mutations within the V3 loop of the viral envelope (Env) protein and was modulated by additional mutations in the V4 loop. Deep sequencing of pretreatment plasma viral RNA indicated that resistance appears to have occurred by evolution of drug-bound CCR5 use, despite the presence of viral sequences predictive of CXCR4 use. Envs obtained from this patient before and during MVC treatment were able to infect cells expressing very low CCR5 levels, indicating highly efficient use of a coreceptor. In contrast to previous reports in which CCR5 antagonist-resistant viruses interact predominantly with the N terminus of CCR5, these MVC-resistant Envs were also dependent upon the drug-modified ECLs of CCR5 for entry. Our results suggest a model of CCR5 cross-resistance whereby viruses that predominantly utilize the N terminus are broadly cross-resistant to multiple CCR5 antagonists, whereas viruses that require both the N terminus and antagonist-specific ECL changes demonstrate a narrow cross-resistance profile.
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