Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells
- PDF / 1,155,591 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 74 Downloads / 193 Views
www.virosin.org www.springer.com/12250
(0123456789().,-volV)(0123456789().,-volV)
RESEARCH ARTICLE
Hepatitis C Virus NS2 Protein Suppresses RNA Interference in Cells Hui Zhou1 • Qi Qian1,2 • Ting Shu2,3 • Jiuyue Xu2,4 • Jing Kong2,4 • Jingfang Mu2 • Yang Qiu2,4 Xi Zhou1,2,4
•
Received: 12 October 2019 / Accepted: 1 November 2019 Ó Wuhan Institute of Virology, CAS 2019
Abstract 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 doublestranded 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 VSR in vitro, thereby providing novel insights into the life cycle and virus-host interactions of HCV. Keywords Hepatitis C virus (HCV) NS2 Antiviral RNAi Viral suppressor of RNAi (VSR)
Introduction HCV is a positive-sense, single-stranded RNA virus that belongs to the genus Hepacivirus of the family Flaviviridae. Its genome is approximately 9.6 kb in length and encodes a polyprotein that is cleaved by host and viral proteases to produce ten mature viral proteins, including structural core protein, envelope proteins E1 and E2, the p7
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12250-019-00182-5) contains supplementary material, which is available to authorized users. & Yang Qiu [email protected] & Xi Zhou [email protected] 1
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China
2
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
3
Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan 430040, China
4
University of Chinese Academy of Sciences, Beijing 100049, China
ion channel protein, and nonstructural (NS) proteins NS2, NS3, NS4A, NS4B, NS5A and NS5B (Yin et al. 2018). HCV infection causes acute and chronic hepatitis in humans with a high propensity for chronicity. A large number of HCV-infected patients fail to clear this virus and remain asymptomatic for years to develop severe liver diseases such as cirrhosis and hepatocellular carcinoma (Paboriboune et al. 2018). The capability of establishing chronic infection by HCV is partly due to its ability to evade host innate immune responses (Horner and Gale 201
Data Loading...
