Alphavirus infection triggers antiviral RNAi immunity in mammals.

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.

• Authors: Jing Kong, Yuanyuan Bie, Wenting Ji, Jiuyue Xu, Bao Lyu, Xiaobei Xiong, Yang Qiu, Xi Zhou
• Journal: Cell reports (Cell Rep) Vol. 42 Issue 5 Pg. 112441 (05 30 2023) ISSN: 2211-1247 [Electronic] United States
• PMID: 37104090 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antiviral Agents
• RNA, Small Interfering

Topics

• Animals
• Mice
• RNA Interference
• Antiviral Agents
• Cell Line
• RNA, Small Interfering (genetics)
• Semliki forest virus (genetics)
• Alphavirus Infections
• Sindbis Virus (genetics)
• Mammals (genetics)
• Virus Replication