2006 Fiscal Year Final Research Report Summary
Analyzing the contribution of intracellular localization of hepatitis C virus replication complex for the drug resistance.
| Project/Area Number |
17590627
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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 | University of Yamanashi |
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Principal Investigator |
MAEKAWA Shinya University of Yamanashi, Graduate School of Medicine and Engineering, Assistant Professor, 大学院医学工学総合研究部, 講師 (70397298)
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| Co-Investigator(Kenkyū-buntansha) |
ENOMOTO Nobuyuki University of Yamanashi, Graduate School of Medicine and Engineering, Professor, 大学院医学工学総合研究部, 教授 (20251530)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Hepatitis C Virus / NS5A protein / HCV replicon / interferon / インターフェロン |
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| Research Abstract |
This research is aimed to disclose the relationship between intracellular localization of hepatitis C virus (HCV) replication complex and the effect of anti-viral drugs such as interferon-alpha, and finally to develop new anti-HCV strategies through understanding of viral replication mechanism(s) in the replication complex.
Recently, micro-domains of organelle membranes rich in sphingomyelin and cholesterol in the form of "lipid rafts" have been considered to act as a scaffold for HCV replication complex formation, indicating the possibility that the lipid raft could be a new therapeutic target. In the present study, we investigated the effect of myriocin, an inhibitor of sphingomyelin synthesis, on HCV replication using an HCV-subgenomic replicon system, as well as the infectious HCV culture system. We also investigated the combined effect of myriocin plus interferon-alpha, or myriocin plus simvastatin, on HCV replication. Myriocin suppressed intracellular RNA replication of both genotype lb subgenomic HCV replicon RNA and genotype 2a infectious HCV RNA in a time-and dose-dependent manner (subgenomic HCV-lb, max. 70% at 120 hours ; genomic HCV-2a, max. 60% at 96 hours). Combination treatment with myriocin plus IFN or simvastatin attenuated intracellular HCV-RNA replication synergistically.
Our data demonstrate that both the sphingomyelin synthesis inhibitor and HMG-CoA inhibitor strongly suppress HCV replication, irrespective of genotype, indicating that the lipid metabolism of the host could be a novel target for HCV therapy.
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[Journal Article] Negative regulation of intracellular hepatitis C virus replication by interferon regulatory factor 3.2006
Author(s)
Yamashiro T, Sakamoto N, Kurosaki M, Kanazawa N, Tanabe Y, Nakagawa M, Chen CH, Itsui Y, Koyama T, Takeda Y, Maekawa S, Enomoto N, Sakugawa H, Watanabe M.
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Journal Title
J Gastroenterol. 41(8)
Pages: 750-7
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis C virus replication.2006
Author(s)
Itsui Y, Sakamoto N, Kurosaki M, Kanazawa N, Tanabe Y, Koyama T, Takeda Y, Nakagawa M, Kakinuma S, Sekine Y, Maekawa S, Enomoto N, Watanabe M.
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Journal Title
J Viral Hepat. 13(10)
Pages: 690-700
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Site-specific mutation of the interferon sensitivity-determining region (ISDR) modulates hepatitis C virus replication.2006
Author(s)
Kohashi T, Maekawa S, Sakamoto N, Kurosaki M, Watanabe H, Tanabe Y, Chen CH, Kanazawa N, Nakagawa M, Kakinuma S, Yamashiro T, Itsui Y, Koyama T, Enomoto N, Watanabe M.
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Journal Title
J Viral Hepat. 13(9)
Pages: 582-90
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Divergent activities of interferon-alpha subtypes against intracellular hepatitis C virus replication2006
Author(s)
Koyama T, Sakamoto N, Tanabe Y, Nakagawa M, Itsui Y, Takeda Y, Kakinuma S, Sekine Y, Maekawa S, Yanai Y, Kurimoto M, Watanabe M.
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Journal Title
Hepatol Res. 34(1)
Pages: 41-9
Description
「研究成果報告書概要(欧文)」より
