VISA is an adapter protein required for virus-triggered IFN-beta signaling.
Viral infection or stimulation of TLR3 triggers signaling cascades, leading to activation of the transcription factors IRF-3 and NF-kappaB, which collaborate to induce transcription of type I interferon (IFN) genes. In this study, we identified a protein termed VISA (for virus-induced signaling adaptor) as a critical component in the IFN-beta ... signaling pathways. VISA recruits IRF-3 to the cytoplasmic viral dsRNA sensor RIG-I. Depletion of VISA inhibits virus-triggered and RIG-I-mediated activation of IRF-3, NF-kappaB, and the IFN-beta promoter, suggesting that VISA plays a central role in virus-triggered TLR3-independent IFN-beta signaling. Our data also indicate that VISA interacts with TRIF and TRAF6 and mediates bifurcation of the TLR3-triggered NF-kappaB and IRF-3 activation pathways. These findings suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral IFN signaling.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Cell Line, DEAD-box RNA Helicases, Humans, Interferon-beta, Molecular Sequence Data, NF-kappa B, Promoter Regions, Genetic, RNA Helicases, Rats, Sequence Alignment, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 6, Tissue Distribution, Toll-Like Receptor 3, Tumor Necrosis Factor-alpha, Viruses
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Cell Line, DEAD-box RNA Helicases, Humans, Interferon-beta, Molecular Sequence Data, NF-kappa B, Promoter Regions, Genetic, RNA Helicases, Rats, Sequence Alignment, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 6, Tissue Distribution, Toll-Like Receptor 3, Tumor Necrosis Factor-alpha, Viruses
Mol. Cell
Date: Sep. 16, 2005
PubMed ID: 16153868
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