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.
Xu
Liang-Guo
LG
Department of Immunology, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, Colorado 80206, USA.
Wang
Yan-Yi
YY
Han
Ke-Jun
KJ
Li
Lian-Yun
LY
Zhai
Zhonghe
Z
Shu
Hong-Bing
HB
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011971:Receptors, Immunologic; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014780:Viruses / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D016899:Interferon-beta; D016328:NF-kappa B; D020365:RNA Helicases; D011971:Receptors, Immunologic; D047992:TNF Receptor-Associated Factor 2; D048029:TNF Receptor-Associated Factor 6; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; C505371:MAVS protein, human; C495344:TLR3 protein, human; C452820:RIGI protein, human; C512612:MAVS protein, mouse