IPS-1, an Adaptor Triggering RIG-I- And Mda5-mediated Type I Interferon Induction

Nat Immunol. 2005 Oct;6(10):981-8. doi: 10.1038/ni1243. Epub 2005 Aug 28.

Abstract

Type I interferons are central mediators for antiviral responses. Using high-throughput functional screening of interferon inducers, we have identified here a molecule we call interferon-beta promoter stimulator 1 (IPS-1). Overexpression of IPS-1 induced type I interferon and interferon-inducible genes through activation of IRF3, IRF7 and NF-kappaB transcription factors. TBK1 and IKKi protein kinases were required for the IPS-1-mediated interferon induction. IPS-1 contained an N-terminal CARD-like structure that mediated interaction with the CARD of RIG-I and Mda5, which are cytoplasmic RNA helicases that sense viral infection. 'Knockdown' of IPS-1 by small interfering RNA blocked interferon induction by virus infection. Thus, IPS-1 is an adaptor involved in RIG-I- and Mda5-mediated antiviral immune responses.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • DNA-Binding Proteins / metabolism
  • Humans
  • I-kappa B Kinase
  • Interferon Inducers / metabolism*
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Interferon Type I / biosynthesis*
  • Interferon-Induced Helicase, IFIH1
  • Interferon-beta / genetics
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / physiology
  • RNA Helicases / metabolism*
  • RNA, Messenger / genetics
  • Sequence Alignment
  • Transcription Factors / metabolism
  • Vesicular stomatitis Indiana virus / immunology
  • Vesicular stomatitis Indiana virus / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • IRF3 protein, human
  • IRF7 protein, human
  • Interferon Inducers
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Interferon Type I
  • Irf3 protein, mouse
  • Irf7 protein, mouse
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factors
  • VISA protein, human
  • Interferon-beta
  • Tbk1 protein, mouse
  • Protein-Serine-Threonine Kinases
  • TBK1 protein, human
  • I-kappa B Kinase
  • DDX58 protein, human
  • IFIH1 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • RNA Helicases