Related Experiment Video

Updated: Jul 27, 2025

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

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

Brian V Tsu1, Rimjhim Agarwal1, Nandan S Gokhale2

  • 1Department of Molecular Biology, University of California, San Diego, La Jolla, California, United States of America.

Plos Biology
|June 8, 2023
PubMed

Insights

Coronaviruses

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Host immune responses involve detecting microbial proteases via inflammasome sensors like NLRP1 and CARD8.
  • Coronaviruses, including SARS-CoV-2, encode 3CL protease (3CLpro) crucial for viral replication.

Purpose of the Study:

  • To investigate the interaction between coronavirus 3CLpro and the human CARD8 inflammasome sensor.
  • To explore how natural variations in CARD8 affect its sensing of viral proteases.

Main Methods:

  • In vitro assays to assess CARD8 cleavage and inflammasome activation by viral proteases.
  • Analysis of CARD8 sequence variation and its functional consequences.

Main Results:

  • Human CARD8 directly cleaves and is activated by coronavirus 3CLpro, triggering inflammasome responses, cell death, and cytokine release during SARS-CoV-2 infection.
  • Natural CARD8 variations alter 3CLpro sensing, with some variants showing antagonism or sensing different viral proteases (e.g., picornavirus 3Cpro).

Conclusions:

  • CARD8 acts as a broad sensor for viral protease activity, including coronavirus 3CLpro.
  • Genetic diversity in CARD8 influences host-virus interactions, contributing to variations in viral sensing and immunopathology across species.

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