Evidence map›Paper›PMID 37289745›Full record

ArticlePLoS biology2023

Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome.

Brian V Tsu, Rimjhim Agarwal, Nandan S Gokhale, Jessie Kulsuptrakul, Andrew P Ryan, Elizabeth J Fay, Lennice K Castro, Christopher Beierschmitt, Christina Yap, Elizabeth A Turcotte and 6 more

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

37 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. NLRP1B is an integrated decoy that subvertsProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Viral effectors trigger innate immunity across the tree of life.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
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  14. Article
  15. Article
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  17. Article
  18. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 1 country.

Brian V TsuDepartment of Molecular Biology, University of California, San Diego, La Jolla, California, United States of America.
Rimjhim AgarwalDepartment of Molecular Biology, University of California, San Diego, La Jolla, California, United States of America.
Nandan S GokhaleDepartment of Immunology, University of Washington; Seattle, Washington, United States of America.
Jessie KulsuptrakulMolecular and Cellular Biology Graduate Program, University of Washington; Seattle, Washington, United States of America.
Andrew P RyanDepartment of Molecular Biology, University of California, San Diego, La Jolla, California, United States of America.
Elizabeth J FayDepartment of Molecular Biology, University of California, San Diego, La Jolla, California, United States of America.
Lennice K CastroDepartment of Molecular Biology, University of California, San Diego, La Jolla, California, United States of America.
Christopher BeierschmittDepartment of Molecular Biology, University of California, San Diego, La Jolla, California, United States of America.
Christina YapDepartment of Microbiology, University of Washington; Seattle, Washington, United States of America.
Elizabeth A TurcotteDivision of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, United States of America.
Sofia E Delgado-RodriguezDepartment of Molecular Biology, University of California, San Diego, La Jolla, California, United States of America.
Russell E VanceDivision of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, California, United States of America.
Jennifer L HydeDepartment of Microbiology, University of Washington; Seattle, Washington, United States of America.
Ram SavanDepartment of Immunology, University of Washington; Seattle, Washington, United States of America.
Patrick S MitchellDepartment of Microbiology, University of Washington; Seattle, Washington, United States of America.ORCID 0000-0001-8375-9060
Matthew D DaughertyDepartment of Molecular Biology, University of California, San Diego, La Jolla, California, United States of America.ORCID 0000-0002-4879-9603
University of California San Diego · USUniversity of Washington · USHoward Hughes Medical Institute · USUniversity of California, Berkeley · US

Funding

The role of Listeria cyclic-di-AMP during infection and immunityP01AI063302 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI PORTNOY, DANIEL A · 2004 to 2025
$45.5M
GENETIC MECHANISMS AND REGULATIONT32GM007240 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMPTON, RANDOLPH Y. · 1985 to 2019
$23.8M
TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
Pathways in Biological Sciences Training ProgramT32GM133351 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Matthew Daugherty, Randolph Y. Hampton · 2020 to 2026
$9.9M
Training in Cellular & Molecular BiologyT32GM136534 · NIGMS · UNIVERSITY OF WASHINGTON · PI Andrew Atwell Oberst, LARRY S ZWEIFEL · 2021 to 2026
$5.8M
Functional and Structural Dissection of Inflammasome ActivationR37AI075039 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI RUSSELL E VANCE · 2018 to 2026
$3.8M
Specificity and in vivo function of the Naip/Nlrc4 inflammasomesR01AI075039 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI VANCE, RUSSELL E · 2008 to 2017
$3.6M
Pathogen-driven evolution of innate antiviral defense mechanismsR35GM133633 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Matthew Daugherty · 2019 to 2026
$3.3M
Translation of evolution-guided insights for new models of human infectious diseaseDP2AI154432 · NIAID · UNIVERSITY OF WASHINGTON · PI MITCHELL, PATRICK S · 2021 to 2025
$2.5M
NIAID NIH HHS DP2 AI154432NIAID NIH HHS P01 AI063302NIAID NIH HHS R01 AI075039NIAID NIH HHS R37 AI075039NIGMS NIH HHS R35 GM133633NIGMS NIH HHS T32 GM007240NIGMS NIH HHS T32 GM007270NIGMS NIH HHS T32 GM133351NIGMS NIH HHS T32 GM136534
6 · The paper itself

Abstract

Hosts have evolved diverse strategies to respond to microbial infections, including the detection of pathogen-encoded proteases by inflammasome-forming sensors such as NLRP1 and CARD8. Here, we find that the 3CL protease (3CLpro) encoded by diverse coronaviruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), cleaves a rapidly evolving region of human CARD8 and activates a robust inflammasome response. CARD8 is required for cell death and the release of pro-inflammatory cytokines during SARS-CoV-2 infection. We further find that natural variation alters CARD8 sensing of 3CLpro, including 3CLpro-mediated antagonism rather than activation of megabat CARD8. Likewise, we find that a single nucleotide polymorphism (SNP) in humans reduces CARD8's ability to sense coronavirus 3CLpros and, instead, enables sensing of 3C proteases (3Cpro) from select picornaviruses. Our findings demonstrate that CARD8 is a broad sensor of viral protease activities and suggests that CARD8 diversity contributes to inter- and intraspecies variation in inflammasome-mediated viral sensing and immunopathology.

Indexed as

COVID-19PicornaviridaeApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsHumansInflammasomesNeoplasm ProteinsProtease InhibitorsSARS-CoV-2Apoptosis Regulatory ProteinsCARD8 protein, humanCARD Signaling Adaptor ProteinsInflammasomesNeoplasm ProteinsProtease Inhibitors

Identifiers

PMID37289745
PMCPMC10249858
OpenAlexW4379932110

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.