1887

Abstract

RNA interference (RNAi) is a potent antiviral defence mechanism in eukaryotes, and numerous viruses have been found to encode viral suppressors of RNAi (VSRs). Coxsackievirus B3 (CVB3) belongs to the genus in the family , and has been reported to be a major causative pathogen for viral myocarditis. Despite the importance of CVB3, it is unclear whether CVB3 can also encode proteins that suppress RNAi. Here, we showed that the CVB3 nonstructural protein 3A suppressed RNAi triggered by either small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. We further uncovered that CVB3 3A interacted directly with double-stranded RNAs (dsRNAs) and siRNAs . Through mutational analysis, we found that the VSR activity of CVB3 3A was significantly reduced by mutations of D24A/L25A/L26A, Y37A/C38A and R60A in conserved residues. In addition, the 3A protein encoded by coxsackievirus B5 (CVB5), another member of , also showed VSR activity. Taken together, our findings showed that CVB3 3A has VSR activity, thereby providing insights into the pathogenesis of CVB3 and other enteroviruses.

Funding
This study was supported by the:
  • xi zhou , National Major Science and Technology Projects of China , (Award 2018ZX10101004)
  • Yang Qiu , National Natural Science Foundation of China , (Award 81873964)
  • Jingfang Mu , National Natural Science Foundation of China , (Award 31800140)
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/content/journal/jgv/10.1099/jgv.0.001434
2020-07-15
2020-12-03
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