National Research Laboratory of Hepatitis C Virus, Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang 431-060, South Korea.
J Virol. 2011 Sep;85(17):8777-88. doi: 10.1128/JVI.02533-10. Epub 2011 Jun 15.
The life cycle of hepatitis C virus (HCV) is highly dependent on cellular factors. Using small interfering RNA (siRNA) library screening, we identified peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) as a host factor involved in HCV propagation. Here we demonstrated that silencing of Pin1 expression resulted in decreases in HCV replication in both HCV replicon cells and cell culture-grown HCV (HCVcc)-infected cells, whereas overexpression of Pin1 increased HCV replication. Pin1 interacted with both the NS5A and NS5B proteins. However, Pin1 expression was increased only by the NS5B protein. Both the protein binding and isomerase activities of Pin1 were required for HCV replication. Juglone, a natural inhibitor of Pin1, inhibited HCV propagation by inhibiting the interplay between the Pin1 and HCV NS5A/NS5B proteins. These data indicate that Pin1 modulates HCV propagation and may contribute to HCV-induced liver pathogenesis.
丙型肝炎病毒 (HCV) 的生命周期高度依赖于细胞因子。通过使用小干扰 RNA (siRNA) 文库筛选，我们发现肽基脯氨酰顺反异构酶 NIMA 相互作用蛋白 1 (Pin1) 是一种参与 HCV 复制的宿主因子。在这里，我们证明沉默 Pin1 的表达会导致 HCV 复制子细胞和细胞培养中感染 HCV (HCVcc) 的细胞中的 HCV 复制减少，而 Pin1 的过表达会增加 HCV 复制。Pin1 与 NS5A 和 NS5B 蛋白相互作用。然而，只有 NS5B 蛋白才能增加 Pin1 的表达。Pin1 的蛋白结合和异构酶活性均对 HCV 复制至关重要。胡桃醌是 Pin1 的天然抑制剂，通过抑制 Pin1 与 HCV NS5A/NS5B 蛋白之间的相互作用来抑制 HCV 的复制。这些数据表明 Pin1 调节 HCV 的复制，并可能导致 HCV 诱导的肝脏发病机制。
