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 Enterovirus in the family Picornaviridae, 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 in vitro. 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 Enterovirus, also showed VSR activity. Taken together, our findings showed that CVB3 3A has in vitro VSR activity, thereby providing insights into the pathogenesis of CVB3 and other enteroviruses.

中文翻译：

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柯萨奇病毒B3的3A蛋白可作为RNA干扰的病毒抑制剂。

RNA干扰（RNAi）是真核生物中有效的抗病毒防御机制，并且发现许多病毒都编码RNAi（VSR）的病毒抑制剂。柯萨奇病毒B3（CVB3）属于肠病毒科Picornaviridae的肠病毒属，据报道是病毒性心肌炎的主要致病菌。尽管CVB3的重要性，目前尚不清楚CVB3是否还可以编码抑制RNAi的蛋白质。在这里，我们表明CVB3非结构蛋白3A抑制了由哺乳动物细胞中的小发夹RNA（shRNA）或小干扰RNA（siRNA）触发的RNAi。我们进一步发现CVB3 3A在体外与双链RNA（dsRNA）和siRNA直接相互作用。通过突变分析，我们发现保守残基中的D24A / L25A / L26A，Y37A / C38A和R60A突变显着降低了CVB3 3A的VSR活性。此外，由肠病毒的另一成员柯萨奇病毒B5（CVB5）编码的3A蛋白也具有VSR活性。综上所述，我们的发现表明CVB3 3A具有体外VSR活性，从而为CVB3和其他肠病毒的发病机理提供了见识。