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

作者：Himanshu Kumar, Taro Kawai, Hiroki Kato, Shintaro Sato, Ken Takahashi, Cevayir Coban, Masahiro Yamamoto, Satoshi Uematsu, Ken J. Ishii, Osamu Takeuchi, Shizuo Akira · 发表于：The Journal of Experimental Medicine · 年份：2006 · DOI：10.1084/jem.20060792 · 被引用次数：505 · 研究领域：interferon and immune responses、Immune Response and Inflammation、Cytokine Signaling Pathways and Interactions

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.