TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response

Kai Yang, He Xin Shi, Xin Yi Liu, Yu Fei Shan, Bo Wei, She Chen, Chen Wang

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Virus infection induces host antiviral responses including induction of type I IFNs. Transcription factor IFN regulatory factor 3 (IRF3) plays an essential role and is tightly regulated in this process. Herein we report that TRIM21 (tripartite motif-containing 21) is significantly induced and interacts with IRF3 upon RNA virus infection. Ectopic expression or knockdown of TRIM21 could respectively enhance or impair IRF3-mediated gene expression. Mechanistically, TRIM21 interferes with the interaction between Pin1 (peptidyl-prolyl cis/trans isomerase, NIMA-interacting 1) and IRF3, thus preventing IRF3 ubiquitination and degradation. A conserved motif in the B 30.2 domain of TRIM21 is critical for its modulation of IRF3 function, while the RING finger is dispensable. Host antiviral responses are significantly boosted or crippled in the presence or absence of TRIM21. Our results identify TRIM21 as an essential modulator of IRF3 stability and demonstrate that it positively regulates the strength and duration of primary antiviral response, thus further strengthening the notion that the TRIM family is evolutionarily integrated with innate immunity.

Original languageEnglish (US)
Pages (from-to)3782-3792
Number of pages11
JournalJournal of Immunology
Volume182
Issue number6
DOIs
StatePublished - Mar 15 2009

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Interferon Regulatory Factor-3
Antiviral Agents
RNA Virus Infections
Ubiquitination
Virus Diseases
Innate Immunity
Transcription Factors
Gene Expression

ASJC Scopus subject areas

  • Immunology

Cite this

TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response. / Yang, Kai; Shi, He Xin; Liu, Xin Yi; Shan, Yu Fei; Wei, Bo; Chen, She; Wang, Chen.

In: Journal of Immunology, Vol. 182, No. 6, 15.03.2009, p. 3782-3792.

Research output: Contribution to journalArticle

Yang, Kai ; Shi, He Xin ; Liu, Xin Yi ; Shan, Yu Fei ; Wei, Bo ; Chen, She ; Wang, Chen. / TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response. In: Journal of Immunology. 2009 ; Vol. 182, No. 6. pp. 3782-3792.
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AU - Chen, She

AU - Wang, Chen

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