Evidence map›Paper›PMID 25980612›Full record

ArticleRetrovirology2015

Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses.

Paul J McLaren, Ali Gawanbacht, Nitisha Pyndiah, Christian Krapp, Dominik Hotter, Silvia F Kluge, Nicola Götz, Jessica Heilmann, Katharina Mack, Daniel Sauter and 7 more

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 5% 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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.

  1. Pooled it
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  15. Transcriptome analysis of CD4Virologica Sinica · 2023
    Article
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  17. Review
  18. The Evolution and Biology of SARS-CoV-2 Variants.Cold Spring Harbor perspectives in medicine · 2022
    Review
  19. Article
  20. Review

5 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

17 authors at 4 institutions in 3 countries.

Paul J McLarenÉcole Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland. paul.mclaren@epfl.ch.
Ali GawanbachtInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. ali.gawanbacht@uni-ulm.de.
Nitisha PyndiahInstitute of Microbiology, University of Lausanne, 1011, Lausanne, Switzerland. nitisha.pyndiah@chuv.ch.
Christian KrappInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. christian.krapp@uni-ulm.de.
Dominik HotterInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. dominik.hotter@uni-ulm.de.
Silvia F KlugeInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. silvia.kluge@uni-ulm.de.
Nicola GötzInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. nicola-goetz@web.de.
Jessica HeilmannInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. Jessica.Heilmann1@gmx.net.
Katharina MackInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. katharina.mack@uni-ulm.de.
Daniel SauterInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. daniel.sauter@uni-ulm.de.
Danielle ThompsonInstitute of Microbiology, University of Lausanne, 1011, Lausanne, Switzerland. Danielle.thompson@unil.ch.
Jérémie PerreaudInstitute of Microbiology, University of Lausanne, 1011, Lausanne, Switzerland. Jeremie.perreaud@unil.ch.
Antonio RausellSwiss Institute of Bioinformatics, 1005, Lausanne, Switzerland. antonio.rausell@isb-sib.ch.
Miguel MunozInstitute of Microbiology, University of Lausanne, 1011, Lausanne, Switzerland. Miguel.munoz@chuv.ch.
Angela CiuffiInstitute of Microbiology, University of Lausanne, 1011, Lausanne, Switzerland. angela.ciuffi@chuv.ch.
Frank KirchhoffInstitute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany. frank.kirchhoff@uni-ulm.de.
Amalio TelentiJ. Craig Venter Institute, La Jolla, , CA 92037, , USA. atelenti@jcvi.org.
Universität Ulm · DEUniversity of Lausanne · CHÉcole Polytechnique Fédérale de Lausanne · CHJ. Craig Venter Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundKnown antiretroviral restriction factors are encoded by genes that are under positive selection pressure, induced during HIV-1 infection, up-regulated by interferons, and/or interact with viral proteins. To identify potential novel restriction factors, we performed genome-wide scans for human genes sharing molecular and evolutionary signatures of known restriction factors and tested the anti-HIV-1 activity of the most promising candidates.

resultsOur analyses identified 30 human genes that share characteristics of known restriction factors. Functional analyses of 27 of these candidates showed that over-expression of a strikingly high proportion of them significantly inhibited HIV-1 without causing cytotoxic effects. Five factors (APOL1, APOL6, CD164, TNFRSF10A, TNFRSF10D) suppressed infectious HIV-1 production in transfected 293T cells by >90% and six additional candidates (FCGR3A, CD3E, OAS1, GBP5, SPN, IFI16) achieved this when the virus was lacking intact accessory vpr, vpu and nef genes. Unexpectedly, over-expression of two factors (IL1A, SP110) significantly increased infectious HIV-1 production. Mechanistic studies suggest that the newly identified potential restriction factors act at different steps of the viral replication cycle, including proviral transcription and production of viral proteins. Finally, we confirmed that mRNA expression of most of these candidate restriction factors in primary CD4+ T cells is significantly increased by type I interferons.

conclusionsA limited number of human genes share multiple characteristics of genes encoding for known restriction factors. Most of them display anti-retroviral activity in transient transfection assays and are expressed in primary CD4+ T cells.

Indexed as

Host-Pathogen InteractionsImmunity, InnateCD4-Positive T-LymphocytesCell LineGene Expression ProfilingGenetic TestingHIV-1Humans

Identifiers

PMID25980612
PMCPMC4434878
OpenAlexW2160102865

What OpenQuestion holds

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Registered trials

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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.