Analysis of virus-induced signaling leading to IRF-3 activation
| Project/Area Number |
15590428
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
YONEYAMA Mitsutoshi Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute of Medical Science, Research Scientist, 東京都臨床医学総合研究所, 主任研究員 (40260335)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Innate Immunity / Type I interferon / Virus / RNA helicase / RNAヘリカーゼ / シグナル伝達 / ウイルス感染 / RIG-I / CARD |
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| Research Abstract |
Innate immunity plays an essential role for eradication of infected viruses. In this work, we analyzed signaling machinery that leads to virus-induced activation of antiviral innate immunity. We identified RNA helicase, retinoic acid inducible gene (RIG)-I, as signaling molecule for virus-induced activation of type I interferon genes, which are known to be critical for antiviral innate immunity. The helicase domain of RIG-I was responsible for recognition of viral double stranded RNA and its intact ATPase activity was essential for signaling. The caspase recruitment domain (CARD) of RIG-I transmitted downstream signals, resulting in the activation of transcription factor, IRF-3, and type I interferon genes. Furthermore, analysis of RIG-I-deficient mice clearly showed the essential role of RIG-I for initiation of antiviral innate immunity. We also determined the function of other RIG-I family helicases, MDA5 and LGP2. Our data indicated that MDA5 acts as positive regulator for virus-induced signal and LGP2 functions as a dominant negative regulator of RIG-I/MDA5-mediated signaling. We are going to examine a molecular mechanism(s) and physiological significance of these helicases in virus-induced signaling.
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Report
(4 results)
Research Products
(35 results)
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[Publications] Mori, M., Yoneyama, M., Ito, T., Takahashi, K., Inagaki, F., Fujita.T.: "Identification of Ser-386 of Interferon Regulatory Factor 3 as Critical Target for Inducible Phosphorylation That Determines Activation"Journal of Biological Chemistry. 279・11. 9698-9702 (2004)
