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

Abstract

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.

• Authors: Himanshu Kumar, Taro Kawai, Hiroki Kato, Shintaro Sato, Ken Takahashi, Cevayir Coban, Masahiro Yamamoto, Satoshi Uematsu, Ken J Ishii, Osamu Takeuchi, Shizuo Akira
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 203 Issue 7 Pg. 1795-803 (Jul 10 2006) ISSN: 0022-1007 [Print] United States
• PMID: 16785313 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• Adaptor Proteins, Signal Transducing (deficiency, genetics, 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)