SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-05-12 DOI:10.1016/j.celrep.2025.115696

Risako Gen, Amin Addetia, Daniel Asarnow, Young-Jun Park, Joel Quispe, Matthew C Chan, Jack T Brown, Jimin Lee, Melody G Campbell, Christopher P Lapointe, David Veesler

{"title":"SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals.","authors":"Risako Gen, Amin Addetia, Daniel Asarnow, Young-Jun Park, Joel Quispe, Matthew C Chan, Jack T Brown, Jimin Lee, Melody G Campbell, Christopher P Lapointe, David Veesler","doi":"10.1016/j.celrep.2025.115696","DOIUrl":null,"url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 in other host species remains elusive, especially in bats-natural reservoirs of sarbecoviruses with a markedly different innate immune system than humans. We reveal that nsp1 potently inhibits translation in Rhinolophus lepidus bat cells, which belong to the same genus as known sarbecovirus reservoir hosts. We determined a cryoelectron microscopy structure of nsp1 bound to the R. lepidus 40S ribosomal subunit, showing that it blocks the mRNA entry channel by targeting a highly conserved site among mammals. Accordingly, we found that nsp1 blocked protein translation in mammalian cells from several species, underscoring its broadly inhibitory activity and conserved role in numerous SARS-CoV-2 hosts. Our findings illuminate the arms race between coronaviruses and mammalian host immunity, providing a foundation for understanding the determinants of viral maintenance in bat hosts and spillover.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115696"},"PeriodicalIF":7.5000,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2025.115696","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 in other host species remains elusive, especially in bats-natural reservoirs of sarbecoviruses with a markedly different innate immune system than humans. We reveal that nsp1 potently inhibits translation in Rhinolophus lepidus bat cells, which belong to the same genus as known sarbecovirus reservoir hosts. We determined a cryoelectron microscopy structure of nsp1 bound to the R. lepidus 40S ribosomal subunit, showing that it blocks the mRNA entry channel by targeting a highly conserved site among mammals. Accordingly, we found that nsp1 blocked protein translation in mammalian cells from several species, underscoring its broadly inhibitory activity and conserved role in numerous SARS-CoV-2 hosts. Our findings illuminate the arms race between coronaviruses and mammalian host immunity, providing a foundation for understanding the determinants of viral maintenance in bat hosts and spillover.

查看原文本刊更多论文

SARS-CoV-2 nsp1介导哺乳动物翻译的广泛抑制。

严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）非结构蛋白1 （nsp1）通过抑制宿主在人类细胞中的翻译促进先天免疫逃避。然而，nsp1在其他宿主物种中的作用仍然难以捉摸，特别是在蝙蝠中——具有与人类明显不同的先天免疫系统的sarbecovirus的天然宿主。我们发现nsp1在鳞翅目鼻蝗蝙蝠细胞中有效抑制翻译，这些细胞与已知的sarbecvirus宿主属于同一属。我们在冷冻电镜下确定了与鳞翅目鼠40S核糖体亚基结合的nsp1的结构，表明它通过靶向哺乳动物中高度保守的位点来阻断mRNA进入通道。因此，我们发现nsp1阻断了几种哺乳动物细胞中的蛋白质翻译，强调了它在许多SARS-CoV-2宿主中的广泛抑制活性和保守作用。我们的发现阐明了冠状病毒与哺乳动物宿主免疫之间的军备竞赛，为理解病毒在蝙蝠宿主中维持和溢出的决定因素提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.