Hepatitis C virus core protein is a potent inhibitor of RNA silencing-based antiviral response.
Hepatitis C virus core protein is a potent inhibitor of RNA silencing-based antiviral response.
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DOI：
10.1053/j.gastro.2005.12.028
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发表时间：
2006-03
期刊：
影响因子：
29.4
通讯作者：
Yue Wang;N. Kato;A. Jazag;N. Dharel;M. Otsuka;Hiroyoshi Taniguchi;T. Kawabe;M. Omata
中科院分区：
文献类型：
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作者：
Yue Wang;N. Kato;A. Jazag;N. Dharel;M. Otsuka;Hiroyoshi Taniguchi;T. Kawabe;M. Omata
背景与目的 丙型肝炎病毒（HCV）持续感染会导致慢性肝炎和肝细胞癌（HCC）。 RNA 干扰 (RNAi) 可能作为宿主针对病毒 RNA 的抗病毒反应。方法采用HCV相关短干扰RNA（siRNA）检测方法研究RNAi对HCV复制中间体和内部核糖体进入位点（IRES）的影响。通过使用 RNAi 检测材料研究了 HCV 逃脱 RNAi 的机制。结果这些研究表明，Dicer（一种生成短 siRNA 的 RNase 酶）可以靶向 IRES 和 HCV 复制中间体并将其消化成大约 22 个核苷酸的 siRNA。进一步的研究还表明Dicer可以抑制HCV亚基因组复制子的复制。然而，HCV 核心蛋白抑制这种 RNAi，并通过与 Dicer 的直接相互作用来拯救 HCV 亚基因组复制子的复制。结论 RNAi是HCV感染的限制因素，核心蛋白抑制基于RNA沉默的抗病毒反应。核心蛋白抵抗宿主防御的这种能力可能导致持续的病毒感染，并可能促进 HCV 的发病机制。
BACKGROUND & AIMS Persistent infection with hepatitis C virus (HCV) leads to chronic hepatitis and hepatocellular carcinoma (HCC). RNA interference (RNAi) may act as a host antiviral response against viral RNA. METHODS The effects of RNAi on both the replicative intermediates and the internal ribosome entry site (IRES) of HCV were studied by using HCV-related short interfering RNA (siRNA) detection assay. The mechanism that permits HCV to escape RNAi was studied by using RNAi assay materials. RESULTS These studies demonstrate that the Dicer, an RNase enzyme that generates short siRNA, can target and digest both the IRES and the replicative intermediate of HCV into siRNA of approximately 22 nucleotides. Further studies also show that Dicer can inhibit the replication of the HCV subgenomic replicon. However, the HCV core protein inhibits this RNAi and rescues the replication of the HCV subgenomic replicon through a direct interaction with Dicer. CONCLUSIONS RNAi is a limiting factor for HCV infection, and the core protein suppresses the RNA silencing-based antiviral response. This ability of the core protein to counteract the host defense may lead to a persistent viral infection and may contribute to the pathogenesis of HCV.