Project/Area Number |
24659371
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Gastroenterology
|
Research Institution | Kagoshima University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
宇都 浩文 鹿児島大学, 大学院・医歯学総合研究科, 講師 (20347058)
|
Research Collaborator |
馬渡 誠一 , 大学院生
|
Project Period (FY) |
2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
|
Keywords | 肝臓学 / HCV / セリンプロテアーゼ / 補体C4 / 断片化 |
Research Abstract |
The mechanisms underlying the persistence of Hepatitis C virus(HCV) infection are hypothesized to involve viral proteins abrogating the host immune response. Here, we report that HCV NS3/4A protease is associated with production of the C4 fragment and that this action affects the host immune response. In vitro, HCV NS3/4A protease showed concentration-dependent cleavage of C4 and a HCV NS3/4A protease inhibitor inhibited this cleavage. Functionally, cleavage of C4by HCV NS3/4A protease inhibited the classical pathway and this inhibition was also abrogated by a HCV NS3/4A protease inhibitor. Our results indicate that HCV NS3/4A protease inhibits complement activation through cleavage of C4, and that C4 cleavage by HCV NS3/4A protease should be one of the mechanisms underlying persistent HCV infection.
|