VISA is an adapter protein required for virus-triggered IFN-beta signaling

Mol Cell. 2005 Sep 16;19(6):727-40. doi: 10.1016/j.molcel.2005.08.014.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Humans
  • Interferon-beta / genetics
  • Interferon-beta / metabolism*
  • Molecular Sequence Data
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic
  • RNA Helicases / genetics
  • RNA Helicases / metabolism
  • Rats
  • Sequence Alignment
  • Signal Transduction / physiology*
  • TNF Receptor-Associated Factor 2 / genetics
  • TNF Receptor-Associated Factor 2 / metabolism
  • TNF Receptor-Associated Factor 6 / genetics
  • TNF Receptor-Associated Factor 6 / metabolism
  • Tissue Distribution
  • Toll-Like Receptor 3 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Viruses / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • NF-kappa B
  • TLR3 protein, human
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptor 3
  • Tumor Necrosis Factor-alpha
  • VISA protein, human
  • VISA protein, mouse
  • Interferon-beta
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • RNA Helicases

Associated data

  • GENBANK/DQ167126
  • GENBANK/DQ167127