The Adaptor Protein MITA Links Virus-Sensing Receptors to IRF3 Transcription Factor Activation

被引：1313

作者：

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
]}

机构：

[1] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China

来源：

IMMUNITY | 2008年 / 29卷 / 04期

基金：

中国国家自然科学基金;

关键词：

D O I：

10.1016/j.immuni.2008.09.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：538 / 550

页数：13

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