A new development of antivirals for eradication of HBV cccDNA
| 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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Report
(4 results)
Research Products
(41 results)
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[Journal Article] Effects of resistance-associated variants in genotype 2 hepatitis C virus on viral replication and susceptibility to antihepatitis C virus drugs.2019
Author(s)
Suda G, Kimura M, Shigesawa T, Suzuki K, Nakamura A, Ohara M, Kawagishi N, Nakai M, Sho T, Maehara O, Shimazaki T, Morikawa K, Natsuizaka M, Ogawa K, Sakamoto N.
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Journal Title
Hepatol Res
Volume: 49
Issue: 11
Pages: 1275-1285
DOI
Related Report
Peer Reviewed
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[Journal Article] Increased serum C-reactive protein and decreased urinary aquaporin 2 levels are predictive of the efficacy of tolvaptan in patients with liver cirrhosis2018
Author(s)
3.Nakai M, Ogawa K, Takeda R, Ohara M, Kawagishi N, Izumi T, Umemura M, Ito J, Sho T, Suda G, Morikawa K, Sakamoto N
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Journal Title
Hepatolgy Research
Volume: in press
Issue: 3
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Hepatitis B virus reactivation during hepatitis C direct-acting antiviral therapy in patients with previous HBV infection2017
Author(s)
Kawagishi N, Suda G, Onozawa M, Kimura M, Maehara O, Ito J, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N
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Journal Title
Journal of Hepatology
Volume: 67
Issue: 5
Pages: 1098-1106
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Long-term effect of nucleos(t)ide analogs on hepatitis B surface antigen in chronic hepatits B patients.2019
Author(s)
1.Morikawa K, Umemura M, Ogawa K, Shigesawa T, Suzuki K, Nakamura A, Ohara M, Kawagishi N, Shimazaki T, Kimura M, Izumi T, Nakai M, Sho T, Suda G, Natsuizaka M, Ono K, Murata K, Sugiyama M, Mizokami M, Sakamoto N.
Organizer
The European Association for the Study of the Liver (EASL) International Liver Congress.
Related Report
Int'l Joint Research
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[Presentation] Risk assessment of hepatocellular carcinoma in chronic liver disease patients with a combination of liver stiffness measurement and controlled attenuation parameter by FibroScan.2018
Author(s)
Morikawa K, Izumi T, Sho T, Suzuki K, Nakamura A, Ohara M, Kawagishi N, Umemura M, Nakai M, Suda G, Ogawa K, Kudo Y, Nishida M, Baba M, Furuya K, Sakamoto N.
Organizer
The European Association for the Study of the Liver (EASL) International Liver Congress.
Related Report
Int'l Joint Research
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[Presentation] Clinical phase 1b study results for safety, pharmacokinetics and efficacy of ND-L02-s0201, a novel targeted lipid nanoparticle delivering HSP47 SIRNA for the treatment of Japanese patients with advanced liver fibrosis.2018
Author(s)
Sakamoto N, Ogawa K, Morikawa K, Suda G, Sho T, Nakai M, Suzuki H, Yamagata N, Tanaka Y, Ying W, Tamura Y, Niitsu Y, Maruyama K.
Organizer
he European Association for the Study of the Liver (EASL) International Liver Congress.
Related Report
Int'l Joint Research
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[Presentation] Prevalence and risk factors of hepatitis B virus reactivation in interferon-free direct-acting antiviral therapies for hepatitis C.2017
Author(s)
Kawagishi N, Suda G, Onozawa M, Kimura M, Maehara O, Ohara M, Izumi T, Umemura M, Ito J, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N.
Organizer
The European Association for the Study of the Liver (EASL) International Liver Congress. (Amsterdam, Netherlands)
Related Report
Int'l Joint Research
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[Presentation] Hepatitis B virus X protein modulates host restriction factor via interaction with DDB1.2017
Author(s)
Izumi T, Morikawa K, Ando S, Takeda R, Umemura M, Shimazaki T, Kawagishi N, Ohara M, Ito J, Nakai M, Sho T, Suda G, Ogawa K, Sakamoto N.
Organizer
The Asian Pacific Association for the Study of the Liver (APASL) Single Topic Conference. (Nagasaki, Japan)
Related Report
Int'l Joint Research
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[Presentation] Influence of hepatitis B virus genotypes on innate immune response by impairing Mitochondrial Antiviral Signaling Protein.2017
Author(s)
Umemura M, Morikawa K, Ando S, Takeda R, Izumi T, Shimazaki T, Kawagishi N, Ohara M, Ito J, Nakai M, Sho T, Suda G, Ogawa K, Sakamoto N.
Organizer
The Asian Pacific Association for the Study of the Liver (APASL) Single Topic Conference. (Nagasaki, Japan)
Related Report
Int'l Joint Research
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[Book] 内科学書2019
Author(s)
森川賢一他
Total Pages
509
Publisher
(株)中山書店
Related Report
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