| 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)
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| 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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