Evidence map›Paper›PMID 24268781›Full record

ArticleCell reports2013

Link between primate lentiviral coreceptor usage and Nef function.

Jan Schmökel, Hui Li, Asma Shabir, Hangxing Yu, Matthias Geyer, Guido Silvestri, Donald L Sodora, Beatrice H Hahn, Frank Kirchhoff

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Review
  3. Loss of Nef-mediated CD3 down-regulation in the HIV-1 lineage increases viral infectivity and spread.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  4. Article
  5. Article
  6. Article
  7. Article
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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

9 authors at 5 institutions in 2 countries.

Jan SchmökelInstitute of Molecular Virology, University of Ulm, 89069 Ulm, Germany.
Hui LiDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Asma ShabirInstitute of Molecular Virology, University of Ulm, 89069 Ulm, Germany.
Hangxing YuInstitute of Molecular Virology, University of Ulm, 89069 Ulm, Germany.
Matthias GeyerCenter of Advanced European Studies and Research (CAESAR), Physical Biochemistry Group, 53175 Bonn, Germany.
Guido SilvestriYerkes Regional Primate Research Center, Emory University, Atlanta, GA 30322, USA.
Donald L SodoraSeattle Biomedical Research Institute, Seattle, WA 98109, USA.
Beatrice H HahnDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Frank KirchhoffInstitute of Molecular Virology, University of Ulm, 89069 Ulm, Germany. Electronic address: frank.kirchhoff@uni-ulm.de.
Universität Ulm · DEUniversity of Pennsylvania · USCenter for Infectious Disease Research · USCenter of Advanced European Studies and Research · DEEmory University · US

Funding

Novel SIVsmm strains for analysis of mucosal transmission and vaccine protectionP01AI088564 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHAW, GEORGE M · 2010 to 2014
$12.7M
Natural SIV Reservoirs and Human Zoonotic RiskR01AI050529 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HAHN, BEATRICE H · 2001 to 2022
$6.1M
Natural SIV Reservoirs and Human Zoonotic RiskR37AI050529 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HAHN, BEATRICE H · 2008 to 2017
$5.7M
Studies of Natural SIV Infection of Sooty MangabeysR01AI066998 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI SILVESTRI, GUIDO · 2006 to 2010
$3.5M
NIAID NIH HHS P01 AI 088564NIAID NIH HHS P01 AI088564NIAID NIH HHS R01 AI 050529NIAID NIH HHS R01 AI050529NIAID NIH HHS R01 AI 066998NIAID NIH HHS R01 AI066998NIAID NIH HHS R37 AI050529
6 · The paper itself

Abstract

Simian immunodeficiency virus (SIVsmm) infection of sooty mangabeys (Cercocebus atys) is characterized by stable CD4(+) T cell counts despite high plasma levels of CCR5-tropic viruses. However, in rare instances, SIVsmm acquires CXCR4 coreceptor tropism and causes severe CD4(+) T cell depletion, albeit without clinical signs of immunodeficiency. Here, we show that CXCR4-tropic SIVsmm strains lost their ability to downmodulate TCR-CD3 by evolving unusual Nef mutations that initially reduced (I132V) and subsequently disrupted (I123L and L146F) interaction with the CD3 ζ chain. This coevolution of Env and Nef function suggests that CD3 downmodulation is advantageous for viral replication in activated CCR5(+) memory T cells, but not in resting naive CXCR4(+) T cells that have not yet undergone TCR-CD3-mediated stimulation. This may explain why HIV-1, which generally lacks the CD3 downmodulation function, commonly switches to CXCR4 usage, whereas this is extremely rare for SIV strains that have retained this Nef activity.

Indexed as

AnimalsAntigen-Presenting CellsCD3 ComplexCD4-Positive T-LymphocytesCells, CulturedCercocebusGene Products, envGene Products, nefHIV-1HIV-2HIV InfectionsImmunologic MemoryLymphocyte ActivationLymphocyte CountMolecular Sequence DataProtein Structure, TertiaryCD3 antigen, zeta chainCD3 ComplexGene Products, envGene Products, nefReceptor-CD3 Complex, Antigen, T-CellReceptors, CCR5Receptors, CXCR4

Identifiers

PMID24268781
PMCPMC4133736
OpenAlexW2082477478

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.