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Immunity. 2017 Jun 20;46(6):992-1004.e5. doi: 10.1016/j.immuni.2017.05.006.

Human Virus-Derived Small RNAs Can Confer Antiviral Immunity in Mammals.

Author information

1
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; Laboratory of RNA Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.
2
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
3
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
4
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China; Laboratory of RNA Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.
5
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
6
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China.
7
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China. Electronic address: qincf@bmi.ac.cn.
8
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China; Laboratory of RNA Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China. Electronic address: zhouxi@wh.iov.cn.

Abstract

RNA interference (RNAi) functions as a potent antiviral immunity in plants and invertebrates; however, whether RNAi plays antiviral roles in mammals remains unclear. Here, using human enterovirus 71 (HEV71) as a model, we showed HEV71 3A protein as an authentic viral suppressor of RNAi during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. These virus-derived siRNAs were produced from viral dsRNA replicative intermediates in a Dicer-dependent manner and loaded into AGO, and they were fully active in degrading cognate viral RNAs. Recombinant HEV71 deficient in 3A-mediated RNAi suppression was significantly restricted in human somatic cells and mice, whereas Dicer deficiency rescued HEV71 infection independently of type I interferon response. Thus, RNAi can function as an antiviral immunity, which is induced and suppressed by a human virus, in mammals.

PMID:
28636969
DOI:
10.1016/j.immuni.2017.05.006
[Indexed for MEDLINE]
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