Elucidation of host innate sensing mechanism for nucleic acid of hepatitis B virus that possibly cause liver cancer
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 |
Research Field |
Gastroenterology
Tumor therapeutics
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Research Institution | Hokkaido University |
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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Report
(3 results)
Research Products
(11 results)
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[Journal Article] The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus2015
Author(s)
Sato S, Li K, Kameyama T, Hayashi T, Ishida Y, Murakami S, Watanabe T, Iijima S, Sakurai Y, Watashi K, Tsutsumi S, Sato Y, Akita H, Wakita T, Rice CM, Harashima H, Kohara M, Tanaka Y, Takaoka A
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Journal Title
Immunity
Volume: 42
Issue: 1
Pages: 123-132
DOI
Related Report
Peer Reviewed / Open Access
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