The Adaptor Protein MITA Links Virus-Sensing Receptors to IRF3 Transcription Factor Activation.
Zhong, Bo 1; Yang, Yan 1; Li, Shu 1; Wang, Yan-Yi 1; Li, Ying 1; Diao, Feici 1; Lei, Caoqi 1; He, Xiao 1; Zhang, Lu 1; Tien, Po 1; Shu, Hong-Bing 1,*
[Article] Immunity. 29(4):538-550, October 2008.

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: Viral infection triggers activation of transcription factors such as NF-[kappa]B 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.

(C) 2008Elsevier, Inc.