VISA is an adapter protein required for virus-triggered IFN-β signaling

被引:1607
作者
Xu, LG
Wang, YY
Han, KJ
Li, LY
Zhai, ZH
Shu, HB
机构
[1] Natl Jewish Med & Res Ctr, Dept Immunol, Denver, CO 80206 USA
[2] Peking Univ, Dept Cell Biol & Genet, Beijing 100871, Peoples R China
[3] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China
关键词
D O I
10.1016/j.molcel.2005.08.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Viral infection or stimulation of TLR3 triggers signaling cascades, leading to activation of the transcription factors IRF-3 and NF-kappa B, which collaborate to induce transcription of type I interferon (IFN) genes. In this study, we identified a protein termed VISA (for virus-induced signaling adaptor) as a critical component in the IFN-beta signaling pathways. VISA recruits IRF-3 to the cytoplasmic viral dsRNA sensor RIG-I. Depletion of VISA inhibits virus-triggered and RIG+ mediated activation of IRF-3, NF-kappa B, and the IFN-beta promoter, suggesting that VISA plays a central role in virus-triggered TLR3-independent IFN-beta signaling. Our data also indicate that VISA interacts with TRIF and TRAF6 and mediates bifurcation of the TLR3-triggered NF-kappa B and IRF-3 activation pathways. These findings suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral IFN signaling.
引用
收藏
页码:727 / 740
页数:14
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