Abstract
Viral infection triggers activation of transcription factors such as NF-κB and IRF3, which collaborate to induce type I interferons (IFNs) and elicit innate antiviral response. Here, we identified MITA as a critical mediator of virus-triggered type I IFN signaling by expression cloning. Overexpression of MITA activated IRF3, whereas knockdown of MITA inhibited virus-triggered activation of IRF3, expression of type I IFNs, and cellular antiviral response. MITA was found to localize to the outer membrane of mitochondria and to be associated with VISA, a mitochondrial protein that acts as an adaptor in virus-triggered signaling. MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex. MITA was phosphorylated by TBK1, which is required for MITA-mediated activation of IRF3. Our results suggest that MITA is a critical mediator of virus-triggered IRF3 activation and IFN expression and further demonstrate the importance of certain mitochondrial proteins in innate antiviral immunity.
Original language | English (US) |
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Pages (from-to) | 538-550 |
Number of pages | 13 |
Journal | Immunity |
Volume | 29 |
Issue number | 4 |
DOIs | |
State | Published - Oct 17 2008 |
Externally published | Yes |
Keywords
- MOLIMMUNO
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases