Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response.
Nature
; 439(7073): 208-11, 2006 Jan 12.
Article
in En
| MEDLINE
| ID: mdl-16306936
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Diseases
/
Interferon Type I
/
TNF Receptor-Associated Factor 3
/
Toll-Like Receptors
/
Immunity, Innate
Limits:
Animals
Language:
En
Journal:
Nature
Year:
2006
Type:
Article
Affiliation country:
United States