ArticleJournal of virology2004
Impact of mutations in the coreceptor binding site on human immunodeficiency virus type 1 fusion, infection, and entry inhibitor sensitivity.
Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 113 citations in OpenAlex.
- HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug.Journal of virology · 2012Trial
- The Phenomenon of Antiretroviral Drug Resistance in the Context of Human Immunodeficiency Virus Treatment: Dynamic and Ever Evolving Subject Matter.Biomedicines · 2024Review
- Peptide Triazole Inhibitors of HIV-1: Hijackers of Env Metastability.Current protein & peptide science · 2023Review
- 2022 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2022Article
- Minding the gap: The impact of B-cell tolerance on the microbial antibody repertoire.Immunological reviews · 2019Review
- 2019 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2019Article
- Article
- Distinct functions for the membrane-proximal ectodomain region (MPER) of HIV-1 gp41 in cell-free and cell-cell viral transmission and cell-cell fusion.The Journal of biological chemistry · 2018Article
- Complex interplay of kinetic factors governs the synergistic properties of HIV-1 entry inhibitors.The Journal of biological chemistry · 2017Article
- Receptor Activation of HIV-1 Env Leads to Asymmetric Exposure of the gp41 Trimer.PLoS pathogens · 2016Article
- Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors.Retrovirology · 2016Article
- V3-independent competitive resistance of a dual-X4 HIV-1 to the CXCR4 inhibitor AMD3100.PloS one · 2014Article
- HIV-1 resistance mechanism to an electrostatically constrained peptide fusion inhibitor that is active against T-20-resistant strains.Antimicrobial agents and chemotherapy · 2013Article
- Sensitivity changes over the course of infection increases the likelihood of resistance against fusion but not CCR5 receptor blockers.AIDS research and human retroviruses · 2012Article
- Review
- Multifaceted mechanisms of HIV-1 entry inhibition by human α-defensin.The Journal of biological chemistry · 2012Article
- HIV-1 antiretroviral drug therapy.Cold Spring Harbor perspectives in medicine · 2012Review
- Article
- 2011 update of the drug resistance mutations in HIV-1.Topics in antiviral medicine · 2011Review
- A novel chimeric protein-based HIV-1 fusion inhibitor targeting gp41 glycoprotein with high potency and stability.The Journal of biological chemistry · 2011Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
An increasingly large number of antiviral agents that prevent entry of human immunodeficiency virus (HIV) into cells are in preclinical and clinical development. The envelope (Env) protein of HIV is the major viral determinant that affects sensitivity to these compounds. To understand how changes in Env can impact entry inhibitor sensitivity, we introduced six mutations into the conserved coreceptor binding site of the R5 HIV-1 strain YU-2 and measured the effect of these changes on CD4 and coreceptor binding, membrane fusion levels and rates, virus infection, and sensitivity to the fusion inhibitors enfuvirtide (T-20) and T-1249, the CCR5 inhibitor TAK-779, and an antibody to CD4. The mutations had little effect on CD4 binding but reduced CCR5 binding to various extents. In general, reductions in coreceptor binding efficiency resulted in slower fusion kinetics and increased sensitivity to TAK-779 and enfuvirtide. In addition, low CCR5 binding usually reduced overall fusion and infection levels. However, one mutation adjacent to the bridging sheet beta21 strand, P438A, had little effect on fusion activity, fusion rate, infectivity, or sensitivity to enfuvirtide or T-1249 despite causing a marked reduction in CCR5 binding and a significant increase in TAK-779 sensitivity. Thus, our findings indicate that changes in the coreceptor binding site of Env can modulate its fusion activity, infectivity, and entry inhibitor sensitivity by multiple mechanisms and suggest that reductions in coreceptor binding do not always result in prolonged fusion kinetics and increased sensitivity to enfuvirtide.
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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.