First Author | Oganesyan G | Year | 2006 |
Journal | Nature | Volume | 439 |
Issue | 7073 | Pages | 208-11 |
PubMed ID | 16306936 | Mgi Jnum | J:245346 |
Mgi Id | MGI:5918298 | Doi | 10.1038/nature04374 |
Citation | Oganesyan G, et al. (2006) Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 439(7073):208-11 |
abstractText | 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. |