2016 Fiscal Year Final Research Report
Analysis of mechanism of HCV particle formation, secretion, and associated cellular factor
| Project/Area Number |
26461021
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Research Collaborator |
WAKITA TAKAJI 国立感染症研究所, 副所長 (40280789)
DATE TOMOKO 国立感染症研究所, ウイルス第二部, 研究員 (40392360)
SHIMAZAKI TOMOE 北海道大学, 医学(系)研究科(研究院), 学術研究員 (40721494)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | C型肝炎ウイルス / GPｘ８ / ウイルス粒子形成 / ウイルス粒子分泌 / 細胞性因子 |
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| Outline of Final Research Achievements |
We identified that Glutachione peroxidase 8 (GPx8), a membrane-associated peroxidase involved in disulfide bond formation in the endoplasmic reticulum, as a novel cellular substrate of the HCV NS3-4A protease. The aim of this study was to analyze the association between GPx8 and HCV life cycle, especially focused on HCV particle formation and assembly. The functional studies of GPx8 on HCV life cycle, involving overexpression and RNA silencing, revealed that GPx8 is a proviral factor involved in viral particle production but not in HCV entry or RNA replication. GPx8 is a proviral host factor cleaved by the HCV NS3-4A protease. Studies investigating the consequences of cleavage for GPx8 function are underway. The identification of novel cellular substrates of the HCV NS3-4A protease should yield new insights into the HCV life cycle and the pathogenesis of hepatitis C and may reveal novel angles for therapeutic intervention.
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| Free Research Field |
肝臓病学
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