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IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction

Nature Immunology volume 6, pages 981–988 (2005)Cite this article

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-β promoter stimulator 1 (IPS-1). Overexpression of IPS-1 induced type I interferon and interferon-inducible genes through activation of IRF3, IRF7 and NF-κB 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.

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Figure 1: Structure and expression of IPS-1.
Figure 2: Activation of type I interferon promoters by IPS-1.
Figure 3: IPS-1 induces antiviral responses.
Figure 4: NF-κB activation and IL-8 induction by IPS-1.
Figure 5: IPS-1 associates with RIG-I, Mda5, FADD and RIP1.
Figure 6: Knockdown of IPS-1 expression by siRNA.

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Acknowledgements

We thank J.L. Pomerantz and T. Miyazaki for suggestions; D.T. Golenbock for plasmids; T. Abe, Y. Matsuura and T. Fujita for viruses; S. Uematsu, M. Yamamoto and Y. Torii for discussions; A. Miyabe, and A. Shibano for technical support; and M. Hashimoto for secretarial assistance.

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Authors and Affiliations

  1. Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan

    Taro Kawai, Shintaro Sato, Ken J Ishii, Osamu Takeuchi & Shizuo Akira

  2. Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan

    Ken Takahashi, Himanshu Kumar, Hiroki Kato, Osamu Takeuchi & Shizuo Akira

  3. The 21st Century COE, Combined Program on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan

    Cevayir Coban & Shizuo Akira

  4. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Sakyoku, Kyoto, 606-8507, Japan

    Ken Takahashi

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Correspondence to Shizuo Akira.

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Supplementary information

Supplementary Fig. 1

Identification of activators for IFN-β promoter. (PDF 59 kb)

Supplementary Table 1

Summary of isolates. (PDF 7 kb)

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Kawai, T., Takahashi, K., Sato, S. et al. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 6, 981–988 (2005). https://doi.org/10.1038/ni1243

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