2007 Fiscal Year Final Research Report Summary
Physiological Function of Virus-induced sigraing for Artivirall mate immunity
| Project/Area Number |
18390156
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Kyoto University |
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Principal Investigator |
YONEYAMA Mitsutoshi Kyoto University, Institute for virus research, Associate Professor (40260335)
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| Co-Investigator(Kenkyū-buntansha) |
FUJITA Takashi Kyoto Uriversity, Institute for virus research, Professor (10156870)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Signal transduction / Virus / Immunology |
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| Research Abstract |
Type I interferon (IFN) plays a critical role in antiviral innate immunity. Virus-infected cells transiently express type I IFNs and confer strong antiviral activities on surrounding cells Via IFN receptor-mediated signaling. In this research, we focused on the function of virus sensor molecules, RIG-I family RNA helicases, which detect viral RNA in cytoplasm to induce IFN gene expression, and analyzed molecular mechanisms underlying activation of RIG-I family-mediated antiviral innate immunity.
1. We analyzed virus-induced activation of type III IFNs. Our data clearly indicated that type III IFNs are regulated by RIG-I-mediated signaling as well as type I IFNs.
2. In order to elucidate a physiological significance of another RIG-I family member, MDA5, we generated and analyzed knockout mice of MDA5 gene, as collaboration with Dr. Shizuo Akira's group in Osaka University. The results showed that MDA5 also plays an essential role in virus-induced activation of IFN genes. However, MDA5 were involved in the detection of different type of viruses including picorna viruses.
3. We tried to generate a novel assay system for RIG-I-mediated signal transduction. The enforced oligomerization of N-terminal CARD of RIG-I clearly activated the identical signaling to natural virus-induced signal. Using this system, we are going to observe the physiological significance of RIG-I- mediated signaling in innate immunity.
4. We analyzed substrate specificity of RIG-I using in vitro assay system. Finally, we identified RIG-I can detect not only 5ppp-dontaining singe stranded RNA but also monophosphate-containing double stranded RNAs. Furthermore, the C-terminal domain of RIG-I was essential for detection of these substrates to initiate antiviral signaling.
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Research Products
(38 results)
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[Book] 炎症と免疫2007
Author(s)
小野口和英, 他
Total Pages
167-172
Publisher
先端医学社
Description
「研究成果報告書概要(和文)」より
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[Book] 蛋白質 核酸 酵素2007
Author(s)
成田亮, 他
Total Pages
1187-1193
Publisher
共立出版
Description
「研究成果報告書概要(和文)」より
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