Trial reportPLoS pathogens2014
Preservation of tetherin and CD4 counter-activities in circulating Vpu alleles despite extensive sequence variation within HIV-1 infected individuals.
Trial report in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- Identifying Conserved Regions in HIV-1 Proteins by Entropy Analysis of Sequence Variability.International journal of molecular sciences · 2026Article
- Single-cell delineation of strain-specific HIV-1 Vif activities using dual reporter sensor cells and live cell imaging.Journal of virology · 2025Article
- Host cell glycosylation selects for infection with CCR5- versus CXCR4-tropic HIV-1.Nature microbiology · 2024Article
- Article
- Article
- Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4Cell reports · 2023Article
- ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4bioRxiv : the preprint server for biology · 2023Article
- Attenuated HIV-1 Nef But Not Vpu Function in a Cohort of Rwandan Long-Term Survivors.Frontiers in virology (Lausanne, Switzerland) · 2022Article
- Detection of the HIV-1 Accessory Proteins Nef and Vpu by Flow Cytometry Represents a New Tool to Study Their Functional Interplay within a Single Infected CD4Journal of virology · 2022Article
- Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C.Frontiers in immunology · 2022Article
- Review
- Differential Vpu-Mediated CD4 and Tetherin Downregulation Functions among Major HIV-1 Group M Subtypes.Journal of virology · 2020Article
- Article
- HIV-1 Vpu is a potent transcriptional suppressor of NF-κB-elicited antiviral immune responses.eLife · 2019Article
- A virus-packageable CRISPR screen identifies host factors mediating interferon inhibition of HIV.eLife · 2018Article
- Preadaptation of Simian Immunodeficiency Virus SIVsmm Facilitated Env-Mediated Counteraction of Human Tetherin by Human Immunodeficiency Virus Type 2.Journal of virology · 2018Article
- HLA-C downregulation by HIV-1 adapts to host HLA genotype.PLoS pathogens · 2018Article
- Functional conservation and coherence of HIV-1 subtype A Vpu alleles.Scientific reports · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The HIV-1 Vpu protein is expressed from a bi-cistronic message late in the viral life cycle. It functions during viral assembly to maximise infectious virus release by targeting CD4 for proteosomal degradation and counteracting the antiviral protein tetherin (BST2/CD317). Single genome analysis of vpu repertoires throughout infection in 14 individuals infected with HIV-1 clade B revealed extensive amino acid diversity of the Vpu protein. For the most part, this variation in Vpu increases over the course of infection and is associated with predicted epitopes of the individual's MHC class I haplotype, suggesting CD8+ T cell pressure is the major driver of Vpu sequence diversity within the host. Despite this variability, the Vpu functions of targeting CD4 and counteracting both physical virus restriction and NF-κB activation by tetherin are rigorously maintained throughout HIV-1 infection. Only a minority of circulating alleles bear lesions in either of these activities at any given time, suggesting functional Vpu mutants are heavily selected against even at later stages of infection. Comparison of Vpu proteins defective for one or several functions reveals novel determinants of CD4 downregulation, counteraction of tetherin restriction, and inhibition of NF-κB signalling. These data affirm the importance of Vpu functions for in vivo persistence of HIV-1 within infected individuals, not simply for transmission, and highlight its potential as a target for antiviral therapy.
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What OpenQuestion holds
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.