Evidence map›Paper›PMID 19461879›Full record

ArticlePLoS pathogens2009

Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion.

Ravindra K Gupta, Stéphane Hué, Torsten Schaller, Ernst Verschoor, Deenan Pillay, Greg J Towers

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.

0numbers the graph read from it
0cells of the map it votes in
139citing papers in PubMed
12.3field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

139 citing papers in PubMed, 181 citations in OpenAlex.

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  16. Medical sciences (Basel, Switzerland) · 2019
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79 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Ravindra K GuptaMedical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.
Stéphane Hué
Torsten Schaller
Ernst Verschoor
Deenan Pillay
Greg J Towers
Medical Research Council · GBUniversity College London · GBBiomedical Primate Research Centre · NL

Funding

Medical Research Council G0801172Medical Research Council G0801172(87743)Medical Research Council G9721629Wellcome Trust 076608Wellcome Trust WT081772MA
6 · The paper itself

Abstract

The recently identified restriction factor tetherin/BST-2/CD317 is an interferon-inducible trans-membrane protein that restricts HIV-1 particle release in the absence of the HIV-1 countermeasure viral protein U (Vpu). It is known that Tantalus monkey CV1 cells can be rendered non-permissive to HIV-1 release upon stimulation with type 1 interferon, despite the presence of Vpu, suggesting species-specific sensitivity of tetherin proteins to viral countermeasures such as Vpu. Here we demonstrate that Tantalus monkey tetherin restricts HIV-1 by nearly two orders of magnitude, but in contrast to human tetherin the Tantalus protein is insensitive to HIV-1 Vpu. We have investigated tetherin's sensitivity to Vpu using positive selection analyses, seeking evidence for evolutionary conflict between tetherin and viral countermeasures. We provide evidence that tetherin has undergone positive selection during primate evolution. Mutation of a single amino acid (showing evidence of positive selection) in the trans-membrane cap of human tetherin to that in Tantalus monkey (T45I) substantially impacts on sensitivity to HIV-1 Vpu, but not on antiviral activity. Finally, we provide evidence that cellular steady state levels of tetherin are substantially reduced by Vpu, and that the T45I mutation abrogates this effect. This study provides evidence that tetherin is important in protecting mammals against viral infection, and that the HIV-1 Vpu-mediated countermeasure is specifically adapted to act against human tetherin. It also emphasizes the power of selection analyses to illuminate the molecular details of host-virus interactions. This work suggests that tetherin binding agents might protect it from viral encoded countermeasures and thus make powerful antivirals.

Indexed as

Selection, GeneticAmino Acid SequenceAmino Acid SubstitutionAnimalsAntigens, CDBayes TheoremBone Marrow Stromal Antigen 2Cell LineChlorocebus aethiopsCysteine Proteinase InhibitorsGPI-Linked ProteinsHIV-1Human Immunodeficiency Virus ProteinsHumansLeupeptinsMembrane GlycoproteinsAntigens, CDbenzyloxycarbonylleucyl-leucyl-leucine aldehydeBone Marrow Stromal Antigen 2BST2 protein, humanCysteine Proteinase InhibitorsGPI-Linked ProteinsHuman Immunodeficiency Virus ProteinsLeupeptinsMembrane GlycoproteinsViral Regulatory and Accessory ProteinsViroporin Proteinsvpu protein, Human immunodeficiency virus 1

Identifiers

PMID19461879
PMCPMC2678251
OpenAlexW2081557334

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.