2009 Fiscal Year Final Research Report
The importance of sphingolipids in Hepatitis C virus replication
| Project/Area Number |
20790715
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Infectious disease medicine
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
HIRATA Yuichi Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 研究員 (50439452)
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| Project Period (FY) |
2008 – 2009
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| Keywords | スフィンゴ脂質 / C型肝炎ウイルス / SPT阻害剤 / 抗HCV剤 |
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| Research Abstract |
It is reported that hepatitis C virus (HCV) replicated on the lipid raft. We previously demonstrated that sphingomyelin contributed to HCV replication via binding HCV-NS5B (RNA dependent RNA polemerase). Here, we found that other sphingolipids contributed to HCV replication as well as sphingomyelin. Futhermore, we showed that sphingolipids activeted RNA dependent RNA polemerase as well as bound it. Using chimeric mice with humanized livers infected by HCV, we also demonstrated that antiviral effect by SPT inhibitor is corelative to the reduction of sphingolipids in the treated chimeric mice liver, indicating that sphingolipids is essential to HCV replication in vivo. These findings will lead to the development of novel drugs to HCV.
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[Journal Article] Pathogenesis of hepatitis C virus infection in Tupaia belangeri.2010
Author(s)
Amako Y, Tsukiyama-Kohara K, Katsume A, Hirata Y, Sekiguchi S, Tobita Y, Hayashi Y, Hishima T, Funata N, Yonekawa H, Kohara M
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Journal Title
J Virol. 84(1)
Pages: 303-11
Peer Reviewed
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[Journal Article] Hepatitis C virus impairs p53 via persistent overexpression of 3beta-hydroxysterol Delta24-reductase.2009
Author(s)
Nishimura T, Kohara M, Izumi K, Kasama Y, Hirata Y, Huang Y, Shuda M, Mukaidani C, Takano T, Tokunaga Y, Nuriya H, Satoh M, Saito M, Kai C, Tsukiyama-Kohara K
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Journal Title
J Biol Chem 284(52)
Pages: 36442-52
Peer Reviewed
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