ArticleProceedings of the National Academy of Sciences of the United States of America2007
HIV-1 escape from the entry-inhibiting effects of a cholesterol-binding compound via cleavage of gp41 by the viral protease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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.
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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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- Characterization of full-length and cytoplasmic tail-truncated envelope glycoproteins incorporated into human immunodeficiency virus (HIV-1) virions and virus-like particles.Journal of virology · 2025Article
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- Inducible cell lines producing replication-defective human immunodeficiency virus particles containing envelope glycoproteins stabilized in a pretriggered conformation.Journal of virology · 2024Article
- The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.PLoS pathogens · 2024Article
- The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.bioRxiv : the preprint server for biology · 2023Article
- Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Conformational States on Infectious Virus Particles.Journal of virology · 2023Article
- Article
- Characterization of Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Variants Selected for Resistance to a CD4-Mimetic Compound.Journal of virology · 2022Article
- Article
- Across the Hall from Pioneers.Viruses · 2021Article
- Cholesterol in the Viral Membrane is a Molecular Switch Governing HIV-1 Env Clustering.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Oregano Oil and Its Principal Component, Carvacrol, Inhibit HIV-1 Fusion into Target Cells.Journal of virology · 2020Article
- The lipid membrane of HIV-1 stabilizes the viral envelope glycoproteins and modulates their sensitivity to antibody neutralization.The Journal of biological chemistry · 2020Article
- HIV-1 Matrix Trimerization-Impaired Mutants Are Rescued by Matrix Substitutions That Enhance Envelope Glycoprotein Incorporation.Journal of virology · 2019Article
- Replication of HIV-1 envelope protein cytoplasmic domain variants in permissive and restrictive cells.Virology · 2019Article
- Structural and Molecular Determinants of Membrane Binding by the HIV-1 Matrix Protein.Journal of molecular biology · 2016Article
- The cytoplasmic tail of retroviral envelope glycoproteins.Progress in molecular biology and translational science · 2015Review
- The frantic play of the concealed HIV envelope cytoplasmic tail.Retrovirology · 2013Review
- Virion stiffness regulates immature HIV-1 entry.Retrovirology · 2013Article
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 4 institutions in 1 country.
Funding
Abstract
HIV-1 virions are highly enriched in cholesterol relative to the cellular plasma membrane. We recently reported that a cholesterol-binding compound, amphotericin B methyl ester (AME), blocks HIV-1 entry and that single amino acid substitutions in the cytoplasmic tail of the transmembrane envelope glycoprotein gp41 confer resistance to AME. In this study, we defined the mechanism of resistance to AME. We observed that the gp41 in AME-resistant virions is substantially smaller than wild-type gp41. Remarkably, we found that this shift in gp41 size is due to cleavage of the gp41 cytoplasmic tail by the viral protease. We mapped the protease-mediated cleavage to two sites in the cytoplasmic tail and showed that gp41 truncations in this region also confer AME resistance. Thus, to escape the inhibitory effects of AME, HIV-1 evolved a mechanism of protease-mediated envelope glycoprotein cleavage used by several other retroviruses to activate envelope glycoprotein fusogenicity. In contrast to the mechanism of AME resistance observed for HIV-1, we demonstrate that simian immunodeficiency virus can escape from AME via the introduction of premature termination codons in the gp41 cytoplasmic tail coding region. These findings demonstrate that in human T cell lines, HIV-1 and simian immunodeficiency virus can evolve distinct strategies for evading AME, reflecting their differential requirements for the gp41 cytoplasmic tail in virus replication. These data reveal that HIV-1 can escape from an inhibitor of viral entry by acquiring mutations that cause the cytoplasmic tail of gp41 to be cleaved by the viral protease.
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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.