Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response

Speaker: 江承堯                                                        Time: 14:00~15:00, March 15, 2006

Commentator: 凌  斌老師                                          Place: Room 601

Abstract:

Antiviral response is a critical defense mechanism for our bodies. Toll-like receptors (TLRs), a member of innate immunity, play an important role in antiviral response. Pervious studies showed that viral nuclear acids strongly induced antiviral type I interferon (IFN) and inflammatory cytokines production via TLRs-dependent and -independent pathways. In this study,¹ the authors demonstrated the involvement of TNF receptor-associated factor 3 (TRAF3) in TLR3 and TLR7/9 signaling pathways and type I IFN production that inhibited virus replication in fibroblast. Furthermore, TRAF3 associated with the TLR adaptors TRIF and IRAK1, and downstream interferon response factor (IRF) kinases TBK1 and IKKε,. In TLRs-induced IRF activation, TRAF3 synergized with TRIF, IRAK1, TBK1, and IKKε that could increase type I IFN promoter activity. However, IRF nuclear translocation was not observed in TFAF3-deficient cells. Protein kinase R(PKR), an intracellular cytoplasmic receptor, is involved in type I IFN production via a TLR-independent pathway.² TRAF3 associated and synergized with PKR that could increase type I IFN promoter activity. Virus could replicate in TRAF3-deficient fibroblast. However, virus replication was inhibited when TRAF3 was restored. These findings indicate that TRAF3 is required for type I IFN production in both TLR-dependent and -independent antiviral pathways.

References:

1.      Oganesyan, G. et al. 2006. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 439:208-11.

2.      Balachandran, S. et al. 2000. Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection. Immunity.13:129-41.