Novel molecular mechanisms of antiviral innate immune response

2014 Fiscal Year Final Research Report

• 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
• Keywords: ウイルス / 自然免疫 / インターフェロン / C型肝炎

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.

Free Research Field

分子生物学