1. Mammalian viral suppressors of RNA interference.
- Author
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Li, Wan-Xiang and Ding, Shou-Wei
- Subjects
- *
EBOLA virus , *RNA viruses , *DOUBLE-stranded RNA , *RNA , *ORTHOMYXOVIRUSES , *CELL culture , *ENDONUCLEASES - Abstract
The antiviral defense directed by the RNAi pathway employs distinct specificity and effector mechanisms compared with other immune responses. The specificity of antiviral RNAi is programmed by siRNAs processed from virus-derived double-stranded RNA by Dicer endonuclease. Argonaute-containing RNA-induced silencing complex loaded with the viral siRNAs acts as the effector to mediate specific virus clearance by RNAi. Recent studies have provided evidence for the production and antiviral function of virus-derived siRNAs in both undifferentiated and differentiated mammalian cells infected with a range of RNA viruses when the cognate virus-encoded suppressor of RNAi (VSR) is rendered nonfunctional. In this review, we discuss the function, mechanism, and evolutionary origin of the validated mammalian VSRs and cell culture assays for their identification. RNA viruses from the Flaviviridae , Nodaviridae , Orthomyxoviridae , and Picornaviridae encode functionally validated viral suppressors of RNAi (VSRs) to promote mammalian cell infection in the presence or absence of the interferon signaling. Therapeutic targeting of closely related human enteroviral VSRs confers protection in mice against lethal challenges, revealing VSRs as a novel class of antiviral drug targets. Validated VSRs from different virus families show no sequence similarity, but all suppress Dicer-dependent production of virus-derived siRNAs by sequestering long dsRNA likely as a homodimer with a similar fold of two antiparallel α-helices, suggesting convergent evolution. Additional families of human RNA viruses, including Ebola virus and SARS-CoV-1 and 2, encode unrelated VSRs awaiting further functional validation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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