Evidence map›Paper›PMID 24356306›Full record

ArticleNature2014

Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection.

Gilad Doitsh, Nicole L K Galloway, Xin Geng, Zhiyuan Yang, Kathryn M Monroe, Orlando Zepeda, Peter W Hunt, Hiroyu Hatano, Stefanie Sowinski, Isa Muñoz-Arias and 1 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 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 663 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
663citing papers in PubMed, 2 pooled it
48.6field-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

663 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,162 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026
    Review
  6. Article
  7. Article
  8. EZH2: an epigenetic governor of T-cell CaCellular & molecular immunology · 2026
    Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. De novo discovery of bicyclic cysteine-rich peptides targeting gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  19. Review
  20. Review

603 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Gilad Doitsh1] Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA [2].
Nicole L K Galloway1] Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA [2].
Xin Geng1] Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA [2].
Zhiyuan YangGladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA.
Kathryn M MonroeGladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA.
Orlando ZepedaGladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA.
Peter W HuntDepartment of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143, USA.
Hiroyu HatanoDepartment of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143, USA.
Stefanie SowinskiGladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA.
Isa Muñoz-AriasGladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA.
Warner C Greene1] Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA [2] Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143, USA [3] Department of Microbiology and Immunology, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143, USA.
Gladstone Institutes · USUniversity of California, San Francisco · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Using NK Cells to eliminate the latent HIV reservoirU19AI096113 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WOELK, CHRISTOPHER H · 2011 to 2015
$39.5M
Microbial Pathogenesis and Host DefenseT32AI060537 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joanne N. Engel · 2004 to 2026
$6.5M
HIV without AIDS: A Radically Different Approach to Help the Developing WorldDP1DA036502 · NIDA · J. DAVID GLADSTONE INSTITUTES · PI GREENE, WARNER C. · 2013 to 2017
$4.9M
HIV-Induced CD4 T-Cell Depletion: An Innate Host Defense Gone Awry?R21AI102782 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI GREENE, WARNER C. · 2012 to 2013
$505k
NCCDPHP CDC HHS 1DP1036502NIAID NIH HHS NIH P30 AI027763NIAID NIH HHS P30 AI027763NIAID NIH HHS R21 AI102782NIAID NIH HHS R21AI102782NIAID NIH HHS T32 AI060537NIAID NIH HHS U19 AI096113NIAID NIH HHS U19AI0961133NIDA NIH HHS DP1 DA036502NIMHD NIH HHS L60 MD003100
6 · The paper itself

Abstract

The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection-CD4 T-cell depletion and chronic inflammation-and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of 'anti-AIDS' therapeutics targeting the host rather than the virus.

Indexed as

Administration, OralAdultAnti-HIV AgentsCaspase 1Caspase 3Caspase InhibitorsCD4-Positive T-LymphocytesCell DeathHIV-1HIV InfectionsHumansInflammasomesInflammationInterleukin-1betaIn Vitro TechniquesLymph NodesAnti-HIV AgentsCaspase 1Caspase 3Caspase InhibitorsInflammasomesInterleukin-1betaProtein Precursors

Identifiers

PMID24356306
PMCPMC4047036
OpenAlexW2153180469

What OpenQuestion holds

Textmetadata
LicenceTDM
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.