ArticleJournal of virology2009
Characterization of a human immunodeficiency virus type 1 V3 deletion mutation that confers resistance to CCR5 inhibitors and the ability to use aplaviroc-bound receptor.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Genomic Evidence for the Nonpathogenic State in HIV-1-Infected Northern Pig-Tailed Macaques.Molecular biology and evolution · 2023Article
- A Novel Point-of-Care BioNanoSensor for Rapid HIV Detection and Treatment Monitoring.Journal of AIDS & clinical research · 2015Article
- Review
- Article
- High-throughput screening and rapid inhibitor triage using an infectious chimeric Hepatitis C virus.PloS one · 2012Article
- Design and characterization of a peptide mimotope of the HIV-1 gp120 bridging sheet.International journal of molecular sciences · 2012Article
- Multiple CCR5 conformations on the cell surface are used differentially by human immunodeficiency viruses resistant or sensitive to CCR5 inhibitors.Journal of virology · 2011Article
- Article
- Article
- 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.Journal of virology · 2010Article
- Distinct molecular pathways to X4 tropism for a V3-truncated human immunodeficiency virus type 1 lead to differential coreceptor interactions and sensitivity to a CXCR4 antagonist.Journal of virology · 2010Article
- Anti-V3 monoclonal antibodies display broad neutralizing activities against multiple HIV-1 subtypes.PloS one · 2010Article
- Epitope switching as a novel escape mechanism of HIV to CCR5 monoclonal antibodies.Antimicrobial agents and chemotherapy · 2010Article
- Profile of maraviroc: a CCR5 antagonist in the management of treatment-experienced HIV patients.HIV/AIDS (Auckland, N.Z.) · 2010Article
- Structure-function analysis of human immunodeficiency virus type 1 gp120 amino acid mutations associated with resistance to the CCR5 coreceptor antagonist vicriviroc.Journal of virology · 2009Article
- Mechanism of human immunodeficiency virus type 1 resistance to monoclonal antibody B12 that effectively targets the site of CD4 attachment.Journal of virology · 2009Article
- Two HIV-1 variants resistant to small molecule CCR5 inhibitors differ in how they use CCR5 for entry.PLoS pathogens · 2009Article
- Pharmacotherapy of HIV-1 Infection: Focus on CCR5 Antagonist Maraviroc.Clinical medicine. Therapeutics · 2009Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The human immunodeficiency virus type 1 (HIV-1) V3 loop is essential for coreceptor binding and principally determines tropism for the CCR5 and CXCR4 coreceptors. Using the dual-tropic virus HIV-1(R3A), we previously made an extensive panel of V3 deletions and identified subdomains within V3 that could differentially mediate R5 and X4 tropism. A deletion of residues 9 to 12 on the N-terminal side of the V3 stem ablated X4 tropism while leaving R5 tropism intact. This mutation also resulted in complete resistance to several small-molecule CCR5 inhibitors. Here, we extend these studies to further characterize a variant of this mutant, Delta9-12a, adapted for growth in CCR5(+) SupT1 cells. Studies using coreceptor chimeras, monoclonal antibodies directed against the CCR5 amino terminus (NT) and extracellular loops, and CCR5 point mutants revealed that, relative to parental R3A, R5-tropic Delta9-12a was more dependent on the CCR5 NT, a region that contacts the gp120 bridging sheet and V3 base. Neutralization sensitivity assays showed that, compared to parental R3A, Delta9-12a was more sensitive to monoclonal antibodies b12, 4E10, and 2G12. Finally, cross-antagonism assays showed that Delta9-12a could use aplaviroc-bound CCR5 for entry. These studies indicate that increased dependence on the CCR5 NT represents a mechanism by which HIV envelopes acquire resistance to CCR5 antagonists and may have more general implications for mechanisms of drug resistance that arise in vivo. In addition, envelopes such as Delta9-12a may be useful for developing new entry inhibitors that target the interaction of gp120 and the CCR5 NT.
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Registered trials
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.