Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response
Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response
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DOI：
10.1038/nature04374
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发表时间：
2006-01-12
期刊：
影响因子：
64.8
通讯作者：
Cheng, GH
中科院分区：
文献类型：
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作者：
Oganesyan, G;Saha, SK;Cheng, GH
I型干扰素(干扰素)的产生是抵御病毒感染的先天防御的关键组成部分(1)。病毒产物通过激活Toll样受体(TLRs)和胞浆内受体，如蛋白激酶R(PKR)(2-12)，诱导强烈的I型干扰素应答。在这里，我们证明了缺乏TRAF3的细胞在由几种不同的TLR激活的I型干扰素反应中存在缺陷。此外，我们发现TRAF3与TLR接头TRIF和IRAK1，以及下游的IRF3/7激酶TBK1和IKK-epsilon有关，这表明TRAF3是TLR接头和下游调节蛋白之间的关键纽带，对IRF的激活至关重要。除了TLR的刺激外，我们还发现TRAF3缺陷的成纤维细胞在直接感染水泡性口炎病毒时I型干扰素反应存在缺陷，这表明TRAF3也是TLR非依赖病毒识别途径的重要组成部分。我们的数据表明，TRAF3是I型干扰素产生和先天抗病毒反应的主要调节因子。
Type I interferon (IFN) production is a critical component of the innate defence against viral infections(1). Viral products induce strong type I IFN responses through the activation of Toll-like receptors (TLRs) and intracellular cytoplasmic receptors such as protein kinase R (PKR)(2-12). Here we demonstrate that cells lacking TRAF3, a member of the TNF receptor-associated factor family, are defective in type I IFN responses activated by several different TLRs. Furthermore, we show that TRAF3 associates with the TLR adaptors TRIF and IRAK1, as well as downstream IRF3/7 kinases TBK1 and IKK-epsilon, suggesting that TRAF3 serves as a critical link between TLR adaptors and downstream regulatory kinases important for IRF activation. In addition to TLR stimulation, we also show that TRAF3-deficient fibroblasts are defective in their type I IFN response to direct infection with vesicular stomatitis virus, indicating that TRAF3 is also an important component of TLR-independent viral recognition pathways. Our data demonstrate that TRAF3 is a major regulator of type I IFN production and the innate antiviral response.