2022 Fiscal Year Final Research Report
Development of novel antiviral therapy targeting hepatitis B virus host restriction factor
| Project/Area Number |
20K08371
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
坂本 直哉 北海道大学, 医学研究院, 教授 (10334418)
須田 剛生 北海道大学, 大学病院, 特任助教 (20447460)
武井 則雄 北海道大学, 医学研究院, 助教 (50523461)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | HBV / 宿主因子 / HBx |
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| Outline of Final Research Achievements |
The aim of this study was to identify and analyze the function of host restriction factors with anti-HBV activity targeting HBV cccDNA. We established a cell line derived from U2-OS cells that can regulate expression of a Myc-tagged protein on HBx in a drug-inducible manner. Proteome analysis of these cells identified SMC5/6, a host restriction factor for HBV, and immuno-precipitation experiments using DDB1 subunits and HBx to recover SMC5/6 by inhibiting HBx binding to DDB1 confirmed the presence of a novel HBx binding region in DDB1. We confirmed the existence of a new HBx binding region in DDB1, which is different from the known region. We also confirmed the inhibition of HBx-DDB1 binding using synthetic peptides bearing the novel binding site.
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| Free Research Field |
消化器病学
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| Academic Significance and Societal Importance of the Research Achievements |
B型肝炎ウイルス（hepatitis B virus: HBV）感染肝細胞核内には、完全閉鎖型二本鎖DNA（covalently closed circular DNA: cccDNA）が形成される。慢性B型肝炎・肝硬変にはインターフェロンおよび核酸アナログ製剤が使用され一定の効果を上げているが、いずれもcccDNAには影響せず、免疫抑制療法および化学療法でのHBV再活性化や発がんのリスクは残存したままとなっている。
本研究により、将来的に抗HBV宿主制限因子をターゲットにした新規治療法の開発と、HBV再活性化予防への貢献、肝臓癌発生・進展および再発阻止に寄与する癌予防医学への貢献が期待される。
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