MERS-CoV is the only lethal human CoV still endemic in the Arabian Peninsula and neither vaccine nor therapeutics against MERS-CoV infection is available. The nsp1 of CoV is thought to be a major virulence factor because it suppresses protein synthesis through the degradation of host mRNA. In contrast, viral RNA circumvents the nsp1-mediated translational shutoff for an efficient propagation. In this study, we identified amino acid residue in MERS-CoV nsp1 that differ from those of SARS-CoV nsp1, and that appear to be crucial for circumventing the translational shutoff. In addition, reverse genetics analysis suggested the presence of a cis-acting element at the 5'-terminus of the nsp1-coding region, which contributes to the specific recognition of viral RNA that is required for an efficient viral replication. Our results suggest the CoVs share a common mechanism for circumventing the nsp1-mediated translational shutoff.

中文翻译：

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MERS冠状病毒nsp1通过与病毒RNA的特异性相互作用参与有效繁殖。

MERS-CoV是阿拉伯半岛上唯一仍是地方性的致命人类CoV，目前尚无针对MERS-CoV感染的疫苗或治疗剂。CoV的nsp1被认为是主要的毒力因子，因为它通过宿主mRNA的降解抑制了蛋白质的合成。相反，病毒RNA绕过了nsp1介导的翻译关闭，从而实现了有效的繁殖。在这项研究中，我们确定了MERS-CoV nsp1中的氨基酸残基与SARS-CoV nsp1中的氨基酸残基不同，并且这些氨基酸残基对于规避翻译关闭至关重要。此外，反向遗传学分析表明在nsp1编码区的5'端存在一个顺式作用元件，这有助于有效识别病毒复制所需的病毒RNA的特异性识别。