2. Academic Validation
  3. Alphavirus infection triggers antiviral RNAi immunity in mammals

Alphavirus infection triggers antiviral RNAi immunity in mammals

  • Cell Rep. 2023 Apr 26;42(5):112441. doi: 10.1016/j.celrep.2023.112441.
Jing Kong 1,  Yuanyuan Bie 1,  Wenting Ji 2,  Jiuyue Xu 1,  Bao Lyu 1,  Xiaobei Xiong 3,  Yang Qiu 4,  Xi Zhou 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
  • 3 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
  • 4 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: yangqiu@wh.iov.cn.
  • 5 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China. Electronic address: zhouxi@wh.iov.cn.
PMID: 37104090 DOI: 10.1016/j.celrep.2023.112441
Abstract

RNA interference (RNAi) is a well-established Antiviral immunity. However, for mammalian somatic cells, Antiviral RNAi becomes evident only when viral suppressors of RNAi (VSRs) are disabled by mutations or VSR-targeting drugs, thereby limiting its scope as a mammalian immunity. We find that a wild-type alphavirus, Semliki Forest virus (SFV), triggers the Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs) in both mammalian somatic cells and adult mice. These SFV-vsiRNAs are located at a particular region within the 5' terminus of the SFV genome, Argonaute loaded, and active in conferring effective anti-SFV activity. Sindbis virus, another alphavirus, also induces vsiRNA production in mammalian somatic cells. Moreover, treatment with enoxacin, an RNAi enhancer, inhibits SFV replication dependent on RNAi response in vitro and in vivo and protects mice from SFV-induced neuropathogenesis and lethality. These findings show that alphaviruses trigger the production of active vsiRNA in mammalian somatic cells, highlighting the functional importance and therapeutic potential of Antiviral RNAi in mammals.

Keywords

CP: Immunology; CP: Microbiology; Semliki Forest virus; alphavirus; antiviral RNAi; innate immunity; viral siRNA.

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