| Project/Area Number |
17K09400
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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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| Research Field |
Gastroenterology
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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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | HBV cccDNA / B型肝炎ウイルス / cccDNA / HBx / DDB1 / 完全排除 |
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| Outline of Final Research Achievements |
HBx hijacks the E3 ubiquitin ligase mechanism and eliminates host restriction factors that suppress cccDNA . We have cloned each genotype (Ae, Bj, C, D) of HBx and co-transfection experiment was performed with DDB1. HBx bound to DDB1 degradated Smc5 / 6 in pan-genotypic manner. We generated a series of DDB1 and its derivatives, thereafter we did immuno-precipitation assay of HBx and a series of DDB1. We observed a strong binding to a region not previously reported in DDB1. Currently, we are aiming to identify a new binding region in DDB1 with HBx and to develop a new antivirals targeting newly identified region in DDB1.
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| Academic Significance and Societal Importance of the Research Achievements |
1) HBV cccDNAの合成機序の解明は、急性感染者の感染排除や慢性感染者の新規cccDNAを再生肝細胞で阻害する事へとつながる重要な役割を果たすと考えられる。2) HBV cccDNAの転写活性機序の解析により、RNA干渉（RNAi）に適した標的部位を同定し、RNAiを用いたウイルスmRNAを直接標的とする治療法の開発への展開へと発展することが期待できる。3) HBV cccDNAの代謝機序を検討することにより、本研究の結果は基礎的解析にとどまらず、HBV cccDNAの排除に関与する宿主因子を増強する新規化合物の探索に重要な役割を果たすと考えられる。
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