Novel molecular mechanisms of antiviral innate immune response
Project/Area Number |
24590570
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Immunology
|
Research Institution | Hokkaido University |
Principal Investigator |
OSHIUMI Hiroyuki 北海道大学, 人獣共通感染症リサーチセンター, 准教授 (50379103)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | ウイルス / 自然免疫 / インターフェロン / C型肝炎 / C型肝炎ウイルス / ユビキチン / I型インターフェロン / RIG-I |
Outline of Final Research Achievements |
Innate immune response is essential for controlling viral infection. Cytoplasmic viral RNA is recognized by RIG-I-like receptors (RLRs) including RIG-I and MDA5. RLRs trigger the signal to induce type I IFN production, which possesses strong antiviral activities. We revealed that the Riplet ubiquitin ligase mediates K63-linked polyubiquitination of RIG-I C-terminal region, resulting in type I IFN expression. Interestingly, we found that Hepatitis C virus, which is a major cause of hepatocellular carcinoma, suppress Riplet activity in order to escape host innate immune response. RIOK3 is a protein kinase, and our study revealed that RIOK3 phosphorylates MDA5 C-terminal region, which resulted in abrogation of MDA5 multimer formation required for type I IFN expression. These findings provided an important insight into the molecular mechanism of antiviral innate immune response.
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Report
(4 results)
Research Products
(17 results)