| Project/Area Number |
21390145
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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 | 財団法人東京都医学総合研究所 (2011)
Tokyo Metropolitan Organization for Medical Research (2009-2010) |
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Principal Investigator |
KOHARA Michinori 財団法人東京都医学総合研究所, ゲノム医科学研究分野, 副参事研究員 (10250218)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA Yuuichi 財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (50439452)
MUNAKATA Tsubasa 財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (50420237)
TOKUNAGA Yuuko 財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (80555011)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2011: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2009: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 細胞 / スフィンゴ脂質 / HCV複製 / 脂質ラフト / RdRp / C型肝炎ウイルス / SPT / 細胞内逆輸送 / 遺伝子複製 / スフィンゴ肪質 |
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| Research Abstract |
Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes encoding sphingomyelin(SM) synthases. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane(DRM) fraction in which HCV replicates. SGMS-1 expression had a strong correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the specific SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.
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