Determination of host factor for hepatitis C virus replication
| Project/Area Number |
16390139
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
KOHARA Michinori Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, Head, 東京都臨床医学総合研究所, 副参事研究員 (10250218)
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| Co-Investigator(Kenkyū-buntansha) |
SHUDA Masahiro Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, Researcher, 東京都臨床医学総合研究所, 研究員 (10356256)
TAKAHASHI Nobuhiro Tokyo University of Agriculture and Technology, Professor, 応用生物科学科, 教授 (80293017)
INOUE Kazuaki Showa University, Assistant Professor, 医学部, 助教授 (90232529)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | Cyclosporin A / Cyclophilin / Hepatitis C virus / Genome replication / Replication inhibitor / 宿主因子 |
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| Research Abstract |
Hepatitis C virus is the most common cause of chronic liver disease. However, the efficacy of currently available treatments is limited. We recently reported the effects of combined interferon-a/cyclosporin A treatment. In the present study, we examined the effects and mechanism of cyclosporin A on HCV replication.
We evaluated the effect of cyclosporin A on the replication of HCV in vitro. The gene expression of three representative cyclophilins (A, B and F) and Pin-1 were knocked down using small interfering RNAs to clarify which cyclophilin(s) is associated with HCV RNA replication.
Interferon-a combined cyclosporin A treatment accelerated the rate of reduction in serum HCV RNA compared to interferon monotherapy. Cyclosporin A and other inhibitors of the peptidyl-prolyl cis-trans isomerase activity of cyclophilins inhibited HCV RNA replication in HCV replicon cells and in a cell culture system. In contrast, FK506 did not have any inhibitory effect on HCV RNA replication.
These findings indicate that cyclophilins are a crucial component of HCV RNA replication in vitro. Furthermore, cyclophilin B, cyclophilin F and other members of the cyclophilins appear to be involved in HCV RNA replication in vitro. Cyclophilins are essential for HCV RNA replication in vitro, and thus their potent inhibitors are promising anti-HCV drugs.
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Report
(3 results)
Research Products
(28 results)
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[Book] 内科2004
Author(s)
井上和明
Total Pages
6
Publisher
南江堂
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