| Project/Area Number |
20590756
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Yamagata University |
|---|
Principal Investigator |
SHO Ri 山形大学, 大学院・医学系研究科, 助教 (80344787)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
WATANABE Hisayoshi 山形大学, 医学部, 講師 (00332536)
SAITO Takafumi 山形大学, 医学部, 准教授 (80250918)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
FUKAO Akira 山形大学, 大学院・医学系研究科, 教授 (80156736)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | C型肝炎ウイルス / RNAi / HCV replicon / 自然免疫 / 脂質代謝 / C型肝炎 / RHAi |
|---|
| Research Abstract |
Hepatitis C virus (HCV) is a major causative agent of chronic liver disease worldwide. However, our understanding of the molecular interaction between HCV and host cells is limited. To efficiently identify the host factors required for HCV replication, we performed a small-scale RNA interference (RNAi) screen in Huh7.5.1 hepatoma cell during its early stage of HCV infection. RNAi screen showed that two siRNAs against IKBb and Mx genes reduced viral infection by 50% or more whereas four siRNAs enhanced infection by 1.5-fold in Huh-7.5.1 cells. Further loss-of-function analysis revealed that silencing of Mx by siRNA or blocking of Mx by mAb caused dose-dependent inhibition of HCV replication, suggesting that Mx plays an important role in HCV infection. Moreover, gain-of-function assay indicated that over-expression of Mx not only enhanced the viral attachment but also increased the viral replication, suggesting that Mx may facilitate HCV infection in vitro through mediating the viral entry. In conclusion, our study provides a novel approach to explore virus-host interaction and to identify potential antiviral targets.
|
