Format

Send to

Choose Destination
Immunity. 2008 Oct 17;29(4):538-50. doi: 10.1016/j.immuni.2008.09.003. Epub 2008 Sep 25.

The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation.

Author information

1
College of Life Sciences, Wuhan University, Wuhan 430072, China.

Abstract

Viral infection triggers activation of transcription factors such as NF-kappaB 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.

Comment in

PMID:
18818105
DOI:
10.1016/j.immuni.2008.09.003
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center