Alphavirus infection triggers antiviral RNAi immunity in mammals
Summary: 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 tha...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723004527 |
| _version_ | 1827958083691741184 |
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| author | Jing Kong Yuanyuan Bie Wenting Ji Jiuyue Xu Bao Lyu Xiaobei Xiong Yang Qiu Xi Zhou |
| author_facet | Jing Kong Yuanyuan Bie Wenting Ji Jiuyue Xu Bao Lyu Xiaobei Xiong Yang Qiu Xi Zhou |
| author_sort | Jing Kong |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-09T15:29:59Z |
| format | Article |
| id | doaj.art-4a18b935f3cc452b85e7cedb43bb9637 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T15:29:59Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4a18b935f3cc452b85e7cedb43bb96372023-04-28T08:55:24ZengElsevierCell Reports2211-12472023-05-01425112441Alphavirus infection triggers antiviral RNAi immunity in mammalsJing Kong0Yuanyuan Bie1Wenting Ji2Jiuyue Xu3Bao Lyu4Xiaobei Xiong5Yang Qiu6Xi Zhou7State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState 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, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding authorState 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723004527CP: ImmunologyCP: Microbiology |
| spellingShingle | Jing Kong Yuanyuan Bie Wenting Ji Jiuyue Xu Bao Lyu Xiaobei Xiong Yang Qiu Xi Zhou Alphavirus infection triggers antiviral RNAi immunity in mammals Cell Reports CP: Immunology CP: Microbiology |
| title | Alphavirus infection triggers antiviral RNAi immunity in mammals |
| title_full | Alphavirus infection triggers antiviral RNAi immunity in mammals |
| title_fullStr | Alphavirus infection triggers antiviral RNAi immunity in mammals |
| title_full_unstemmed | Alphavirus infection triggers antiviral RNAi immunity in mammals |
| title_short | Alphavirus infection triggers antiviral RNAi immunity in mammals |
| title_sort | alphavirus infection triggers antiviral rnai immunity in mammals |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723004527 |
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