Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells
Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells
复制标题
丙型肝炎病毒 NS2 蛋白抑制细胞中的 RNA 干扰
DOI：
10.1007/s12250-019-00182-5
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发表时间：
2020
影响因子：
5.5
通讯作者：
Zhou Xi
中科院分区：
文献类型：
--
作者：
Zhou Hui;Qian Qi;Shu Ting;Xu Jiuyue;Kong Jing;Mu Jingfang;Qiu Yang;Zhou Xi
RNAi干扰(RNAi)是一种进化保守的转录后基因沉默机制，已被公认为真核生物中一种重要的抗病毒免疫机制。许多病毒已被证明编码RNAi的病毒抑制物(VSR)来拮抗抗病毒RNAi。丙型肝炎病毒是一种医学上重要的人类病原体，可引起急性和慢性肝炎。在本研究中，我们筛选了所有丙型肝炎病毒的非结构蛋白，发现丙型肝炎病毒NS2可以抑制哺乳动物细胞中由小发夹RNA(ShRNAs)或小干扰RNAs(SiRNAs)诱导的RNAi。此外，我们还证明了NS2可以通过与双链RNAs(DsRNAs)和siRNAs的直接相互作用来抑制RNAi，并通过一系列的点突变分析进一步证实了NS2的半胱氨酸184是抑制RNAi活性所必需的。总之，我们的发现揭示了丙型肝炎病毒NS2在体外可以作为VSR，从而为了解丙型肝炎病毒的生命周期和病毒与宿主的相互作用提供了新的见解。
RNAi interference (RNAi) is an evolutionarily conserved post-transcriptional gene silencing mechanism and has been well recognized as an important antiviral immunity in eukaryotes. Numerous viruses have been shown to encode viral suppressors of RNAi (VSRs) to antagonize antiviral RNAi. Hepatitis C virus (HCV) is a medically important human pathogen that causes acute and chronic hepatitis. In this study, we screened all the nonstructural proteins of HCV and found that HCV NS2 could suppress RNAi induced either by small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. Moreover, we demonstrated that NS2 could suppress RNAi via its direct interaction with double-stranded RNAs (dsRNAs) and siRNAs, and further identified that the cysteine 184 of NS2 is required for the RNAi suppression activity through a serial of point mutation analyses. Together, our findings uncovered that HCV NS2 can act as a VSRin vitro, thereby providing novel insights into the life cycle and virus-host interactions of HCV.