Essential role of IPS-1 in innate immune responses against RNA viruses

J Exp Med. 2006 Jul 10;203(7):1795-803. doi: 10.1084/jem.20060792. Epub 2006 Jun 19.


IFN-beta promoter stimulator (IPS)-1 was recently identified as an adapter for retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda5), which recognize distinct RNA viruses. Here we show the critical role of IPS-1 in antiviral responses in vivo. IPS-1-deficient mice showed severe defects in both RIG-I- and Mda5-mediated induction of type I interferon and inflammatory cytokines and were susceptible to RNA virus infection. RNA virus-induced interferon regulatory factor-3 and nuclear factor kappaB activation was also impaired in IPS-1-deficient cells. IPS-1, however, was not essential for the responses to either DNA virus or double-stranded B-DNA. Thus, IPS-1 is the sole adapter in both RIG-I and Mda5 signaling that mediates effective responses against a variety of RNA viruses.

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Cells, Cultured
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Immunity, Innate* / genetics
  • Interferon-Induced Helicase, IFIH1
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic
  • RNA Helicases / physiology
  • RNA Viruses / immunology*
  • Signal Transduction / physiology


  • Adaptor Proteins, Signal Transducing
  • IPS-1 protein, mouse
  • MAVS protein, human
  • Ddx58 protein, mouse
  • Ifih1 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • RNA Helicases