Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase
Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase
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DOI：
10.1016/j.molcel.2005.05.014
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发表时间：
2005-07-01
期刊：
影响因子：
16
通讯作者：
Shimotohno, K
中科院分区：
文献类型：
--
作者：
Watashi, K;Ishii, N;Shimotohno, K
病毒依赖于宿主来源的因子进行有效的基因组复制。在这里，我们证明了细胞的肽基脯氨酰顺反异构酶（PPlase），亲环素B（CyPB），是丙型肝炎病毒（HCV）基因组的有效复制的关键。CyPB与HCV RNA聚合酶NS5B相互作用，直接刺激其RNA结合活性。RNA干扰（RNAi）介导的内源性CyPB表达的降低和诱导的NS5B与CyPB结合的丧失都降低了HCV复制水平。因此，CyPB在HCV复制机制中作为NS5B的刺激性调节剂发挥作用。这种病毒复制的调节机制将CyPB确定为抗病毒治疗策略的靶点。
Viruses depend on host-derived factors for their efficient genome replication. Here, we demonstrate that a cellular peptidyl-prolyl cis-trans isomerase (PPlase), cyclophilin B (CyPB), is critical for the efficient replication of the hepatitis C virus (HCV) genome. CyPB interacted with the HCV RNA polymerase NS5B to directly stimulate its RNA binding activity. Both the RNA interference (RNAi)-mediated reduction of endogenous CyPB expression and the induced loss of NS5B binding to CyPB decreased the levels of HCV replication. Thus, CyPB functions as a stimulatory regulator of NS5B in HCV replication machinery. This regulation mechanism for viral replication identifies CyPB as a target for antiviral therapeutic strategies.