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TRIM21 Regulates Virus-Induced Cell Pyroptosis through Polyubiquitination of ISG12a

Mengmeng Guo1, Wenyan Cao1, Shengwen Chen1

  • 1Institute of Pathogen Biology and Immunology of College of Biology, Hunan Provincial Key Laboratory of Medical Virology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha, China.

Journal of Immunology (Baltimore, Md. : 1950)
|November 25, 2022
PubMed

Insights

Tripartite motif 21 (TRIM21) and interferon-stimulated gene 12a (ISG12a) interact during viral infection, triggering cell pyroptosis. This pathway involves caspase 3 activation and Gasdermin E cleavage, offering new insights into antiviral defense mechanisms.

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Pyroptosis is a critical cell death pathway during viral infections, essential for controlling viral replication.
  • The roles of Tripartite Motif (TRIM) proteins and Interferon-Stimulated Genes (ISGs) in antiviral defense are established, but their specific involvement in pyroptosis is not fully understood.

Purpose of the Study:

  • To elucidate the novel mechanism by which TRIM proteins and ISGs regulate virus-induced pyroptosis.
  • To investigate the interaction between TRIM21 and ISG12a in the context of viral infection and pyroptosis.

Main Methods:

  • Co-immunoprecipitation assays to confirm TRIM21 and ISG12a interaction.
  • Ubiquitination assays to assess ISG12a modification.
  • Mitochondrial translocation studies.
  • Caspase 3 activity assays.
  • Gasdermin E (GSDME) cleavage analysis.

Main Results:

  • TRIM21 was found to interact with ISG12a during viral infection.
  • TRIM21 promotes the ubiquitination of ISG12a, facilitating its translocation into mitochondria.
  • This process leads to caspase 3 activation.
  • Activated caspase 3 specifically cleaves Gasdermin E (GSDME), initiating pyroptosis.

Conclusions:

  • TRIM21 and ISG12a constitute a novel pathway regulating virus-induced pyroptosis.
  • This mechanism highlights a new aspect of the innate immune response to viral pathogens.
  • Targeting the TRIM21-ISG12a-caspase 3 axis could offer therapeutic strategies against viral infections.

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