| Project/Area Number |
25870015
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
Tumor therapeutics
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| Research Institution | Hokkaido University |
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Principal Investigator |
SATO Seiichi 北海道大学, 遺伝子病制御研究所, 助教 (60459724)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | B型肝炎ウイルス / 自然免疫応答 / 核酸センサー / 抗ウイルス因子 / インターフェロン / RIG-I / シグナル伝達 / 肝臓癌 / 核酸 / ウイルス複製 / サイトカイン / 自然免疫 / HBV |
|---|
| Outline of Final Research Achievements |
In this study, we have revealed that HBV infection is sensed by the RIG-I protein through its recognition of certain viral RNA (pregenomic RNA) within the cells, which triggers a predominant production of type III interferons, a well-known antiviral protein. We further determined that a key element for the RIG-I-mediated recognition is the 5′-ε region of HBV pregenomic RNA, which was previously reported to take a stem-loop structure and serve as a binding site of HBV polymerase, an essential enzyme for viral propagation. In relation to this, we also discovered a novel role of RIG-I as a direct antiviral factor that can competitively inhibit the interaction of HBV polymerase with the 5′-ε region of viral genome. These findings indicated that RIG-I dually functions not only as an HBV sensor but also as a counteractor against viral polymerase in human hepatocyte, and also suggest that the ε region-derived RNA would be a therapeutic tool for the treatment of HBV infection.
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