Essential role of IPS-1 in innate immune responses against RNA viruses.
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.
Kumar
Himanshu
H
Department of Host Defense, Japan Science and Technology Agency, Osaka 565-0871, Japan.
Kawai
Taro
T
Kato
Hiroki
H
Sato
Shintaro
S
Takahashi
Ken
K
Coban
Cevayir
C
Yamamoto
Masahiro
M
Uematsu
Satoshi
S
Ishii
Ken J
KJ
Takeuchi
Osamu
O
Akira
Shizuo
S
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D007113:Immunity, Innate / Q000235:genetics; D000072640:Interferon-Induced Helicase, IFIH1; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D020365:RNA Helicases / Q000502:physiology; D012328:RNA Viruses / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases; C512612:MAVS protein, mouse; C505371:MAVS protein, human; C503356:Ddx58 protein, mouse; C510592:Ifih1 protein, mouse