HCV core protein interacts with Dicer to antagonize RNA silencing
HCV core protein interacts with Dicer to antagonize RNA silencing
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HCV核心蛋白与Dicer相互作用拮抗RNA沉默
DOI：
10.1016/j.virusres.2008.01.011
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发表时间：
2008-05-01
期刊：
影响因子：
5
通讯作者：
Huang, Ailong
中科院分区：
文献类型：
--
作者：
Chen, Weixian;Zhang, Zhenzhen;Huang, Ailong
RNA沉默是植物和无脊椎动物中针对病毒的一种基于核酸的免疫形式。成功的病毒感染需要逃避或抑制基因沉默。在这里，我们报告，丙型肝炎病毒（HCV）的核心蛋白作为一个有效的抑制RNA沉默（SRS）。我们已经发现，HCV核心蛋白抑制RNA沉默诱导的短发夹RNA（shRNA），但不是由合成的小干扰RNA（siRNA）在各种哺乳动物细胞。我们进一步证明了HCV核心蛋白直接与Dicer相互作用，Dicer是一种在宿主细胞中产生siRNA的RNA酶。已显示HCV核心蛋白抑制Dicer将双链RNA（dsRNA）加工成siRNA的功能。通过缺失分析，我们发现N端结构域是核心蛋白拮抗Dicer酶RNA沉默活性所必需的。因此，我们的研究结果表明，HCV核心蛋白可能通过抑制Dicer将前体dsRNA加工成siRNA的能力来消除宿主细胞的RNA沉默防御。核心蛋白的这种抗Dicer能力可能与HCV的持续感染和致病有关。(c)2008 Elsevier B.V.保留所有权利。
RNA silencing is a form of nucleic acid-based immunity against viruses in plants and invertebrate animals. Successful viral infection requires evasion or suppression of gene silencing. Here, we report that the core protein of Hepatitis C virus (HCV) acts as a potent suppressor of RNA silencing (SRS). We have found that the HCV core protein inhibits RNA silencing induced by short hairpin RNAs (shRNAs) but not by synthetic small interfering RNAs (siRNAs) in various mammalian cells. We have further demonstrated that HCV core protein directly interacts with Dicer, an RNase enzyme that generates siRNA in host cells. The HCV core protein has been shown to inhibit the function of Dicer to process double-stranded RNAs (dsRNAs) into siRNAs. Through deletion analysis, we have found that the N-terminal domain is required for core protein to antagonize RNA silencing activity of Dicer enzyme. Thus, our results suggest that HCV core protein may abrogate host cell RNA silencing defense by suppressing the ability of Dicer to process precursor dsRNAs into siRNAs. This anti-Dicer ability of core protein may contribute to the persistent viral infection and pathogenesis of HCV. (c) 2008 Elsevier B.V. All rights reserved.