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- Title
Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response.
- Authors
Oganesyan, Gagik; Saha, Supriya K; Guo, Beichu; He, Jeannie Q; Shahangian, Arash; Zarnegar, Brian; Perry, Andrea; Cheng, Genhong
- Abstract
Type I interferon (IFN) production is a critical component of the innate defence against viral infections. 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). 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.
- Publication
Nature, 2006, Vol 439, Issue 7073, p208
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature04374