VISA is an adapter protein required for virus-triggered IFN-beta signaling.
VISA is an adapter protein required for virus-triggered IFN-beta signaling.
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发表时间：
2005
期刊：
影响因子：
16
通讯作者：
Liang-Guo Xu;Yan-Yi Wang;Ke-jun Han;Lianyun Li;Z. Zhai;H. Shu
中科院分区：
文献类型：
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作者：
Liang-Guo Xu;Yan-Yi Wang;Ke-jun Han;Lianyun Li;Z. Zhai;H. Shu
病毒感染或刺激TLR3触发信号级联反应，导致转录因子IRF-3和NF-kappaB的激活，共同诱导I型干扰素(IFN)基因的转录。在这项研究中，我们发现了一种名为VISA(病毒诱导信号适配器)的蛋白质，它是干扰素-β信号通路中的关键成分。Visa将IRF-3招募到细胞质病毒dsRNA传感器RIG-I中。VISA的缺失抑制了病毒触发和RIG-I介导的IRF-3、NF-kappaB和干扰素-β启动子的激活，表明VISA在病毒触发的TLR3非依赖的干扰素-β信号转导中发挥核心作用。我们的数据还表明，VISA与TRIF和TRAF6相互作用，并介导TLR3触发的NF-kappaB和IRF-3激活通路的分叉。这些发现表明，VISA在病毒触发的TLR3非依赖和TLR3介导的抗病毒干扰素信号转导中都起着至关重要的作用。
Viral infection or stimulation of TLR3 triggers signaling cascades, leading to activation of the transcription factors IRF-3 and NF-kappaB, 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-I-mediated activation of IRF-3, NF-kappaB, 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-kappaB 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.