2006 Fiscal Year Final Research Report Summary
Comprehensive screening of host proteins that suppress replication of HCV replicon
| Project/Area Number |
17590626
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SAKAMOTO Naoya Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Associate Professor, 大学院医歯学総合研究科, 助教授 (10334418)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Mamoru Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Professor, 大学院医歯学総合研究科, 教授 (10175127)
ENOMOTO Nobuyuki University of Yamanashi, Faculty of Medicine, Professor, 医学部, 教授 (20251530)
NAKAGAWA Mina Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Instructor, 大学院医歯学総合研究科, 寄付講座教員 (30401342)
ITSUI Yasuhiro Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Fellow, 大学院医歯学総合研究科, 医員 (20401341)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Hepatitis C virus / HCV replicon system / Cyclosporin A / Interferon-stimulated genes / type-I interferon / high-throughput screening |
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| Research Abstract |
We have conducted studies of comprehensive screening of host proteins that suppress hepatitis C virus (HCV) replication using HCV subgenomic replication models and cell culture models.
(1) High throughput screening of a library of 2,500 bioactive drugs, peptides, and compounds : we found 52 compounds that suppress or augment HCV replication (Gastroenterology 2006).
(2) Establishment of antiviral therapies that target molecular chaperone and cyclophillin : we have reported that cyclosporine A suppress HCV replication through blockade of action of cyclophiline A, B and C. In this study, we next screened host proteins that interact with cyclophillins by bacterial two-hybrid system assay, and identified several proteins including G-protein coupled protein. We are now conducting studies to investigate functions of the proteins.
(3) Screening of interferon-stimulated genes that suppress HCV replication : type-I interferon is a key molecule to mediate host virus defense functions. We have newly identified that three IGSs, GBP1, IFI27 and IFI6-16, show suppressive effects on HCV replication. Through immune precipitation assay, we have found that GBP-1 specifically binds HCV-NS5B RNA polymerase.
With the above result we are now further conduct screening of antiviral compounds. These results may contribute to establish novel antiviral therapeutics.
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[Journal Article] Suppression of hepatitis C virus replication by cyclosporin A is mediated by blockage of cyclophilins.2005
Author(s)
Nakagawa M, Sakamoto N (equal contribution), Tanabe Y, Koyama T.Itsui Y, Takeda Y, Chen CH, Kakinuma S, Oooka S, Maekawa S, Enomoto N, Watanabe M
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Journal Title
Gastroenterology. 129(3)
Pages: 1031-1041
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Enhancement of Mitochondrial Gene Expression in the Liver of Primary Biliary Cirrhosis.2005
Author(s)
Chen CH, Nagayama K, Enomoto N, Miyasaka Y, Kurosaki M, Sakamoto N, Meakawa S, Kakinuma S, Ideda T, Izumi N, Sato C, Watanabe M
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Journal Title
Hepatology Res. 31
Pages: 24-30
Description
「研究成果報告書概要(欧文)」より
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