Emergence of SARS-CoV-2 subgenomic RNAs that enhance viral fitness and immune evasion.

IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences PLoS Biology Pub Date : 2025-01-21 DOI:10.1371/journal.pbio.3002982
Harriet V Mears, George R Young, Theo Sanderson, Ruth Harvey, Jamie Barrett-Rodger, Rebecca Penn, Vanessa Cowton, Wilhelm Furnon, Giuditta De Lorenzo, Marg Crawford, Daniel M Snell, Ashley S Fowler, Anob M Chakrabarti, Saira Hussain, Ciarán Gilbride, Edward Emmott, Katja Finsterbusch, Jakub Luptak, Thomas P Peacock, Jérôme Nicod, Arvind H Patel, Massimo Palmarini, Emma Wall, Bryan Williams, Sonia Gandhi, Charles Swanton, David L V Bauer
{"title":"Emergence of SARS-CoV-2 subgenomic RNAs that enhance viral fitness and immune evasion.","authors":"Harriet V Mears, George R Young, Theo Sanderson, Ruth Harvey, Jamie Barrett-Rodger, Rebecca Penn, Vanessa Cowton, Wilhelm Furnon, Giuditta De Lorenzo, Marg Crawford, Daniel M Snell, Ashley S Fowler, Anob M Chakrabarti, Saira Hussain, Ciarán Gilbride, Edward Emmott, Katja Finsterbusch, Jakub Luptak, Thomas P Peacock, Jérôme Nicod, Arvind H Patel, Massimo Palmarini, Emma Wall, Bryan Williams, Sonia Gandhi, Charles Swanton, David L V Bauer","doi":"10.1371/journal.pbio.3002982","DOIUrl":null,"url":null,"abstract":"<p><p>Coronaviruses express their structural and accessory genes via a set of subgenomic RNAs, whose synthesis is directed by transcription regulatory sequences (TRSs) in the 5' genomic leader and upstream of each body open reading frame. In SARS-CoV-2, the TRS has the consensus AAACGAAC; upon searching for emergence of this motif in the global SARS-CoV-2 sequences, we find that it evolves frequently, especially in the 3' end of the genome. We show well-supported examples upstream of the Spike gene-within the nsp16 coding region of ORF1b-which is expressed during human infection, and upstream of the canonical Envelope gene TRS, both of which have evolved convergently in multiple lineages. The most frequent neo-TRS is within the coding region of the Nucleocapsid gene, and is present in virtually all viruses from the B.1.1 lineage, including the variants of concern Alpha, Gamma, Omicron and descendants thereof. Here, we demonstrate that this TRS leads to the expression of a novel subgenomic mRNA encoding a truncated C-terminal portion of Nucleocapsid, which is an antagonist of type I interferon production and contributes to viral fitness during infection. We observe distinct phenotypes when the Nucleocapsid coding sequence is mutated compared to when the TRS alone is ablated. Our findings demonstrate that SARS-CoV-2 is undergoing evolutionary changes at the functional RNA level in addition to the amino acid level.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002982"},"PeriodicalIF":9.8000,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PLoS Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1371/journal.pbio.3002982","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Agricultural and Biological Sciences","Score":null,"Total":0}
引用次数: 0

Abstract

Coronaviruses express their structural and accessory genes via a set of subgenomic RNAs, whose synthesis is directed by transcription regulatory sequences (TRSs) in the 5' genomic leader and upstream of each body open reading frame. In SARS-CoV-2, the TRS has the consensus AAACGAAC; upon searching for emergence of this motif in the global SARS-CoV-2 sequences, we find that it evolves frequently, especially in the 3' end of the genome. We show well-supported examples upstream of the Spike gene-within the nsp16 coding region of ORF1b-which is expressed during human infection, and upstream of the canonical Envelope gene TRS, both of which have evolved convergently in multiple lineages. The most frequent neo-TRS is within the coding region of the Nucleocapsid gene, and is present in virtually all viruses from the B.1.1 lineage, including the variants of concern Alpha, Gamma, Omicron and descendants thereof. Here, we demonstrate that this TRS leads to the expression of a novel subgenomic mRNA encoding a truncated C-terminal portion of Nucleocapsid, which is an antagonist of type I interferon production and contributes to viral fitness during infection. We observe distinct phenotypes when the Nucleocapsid coding sequence is mutated compared to when the TRS alone is ablated. Our findings demonstrate that SARS-CoV-2 is undergoing evolutionary changes at the functional RNA level in addition to the amino acid level.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
增强病毒适应性和免疫逃避的SARS-CoV-2亚基因组rna的出现
冠状病毒通过一组亚基因组rna表达其结构和辅助基因,其合成受5'基因组先导和每个体开放阅读框上游的转录调控序列(TRSs)的指导。在SARS-CoV-2中,TRS具有共识AAACGAAC;通过在全球SARS-CoV-2序列中搜索该基序的出现,我们发现它进化频繁,特别是在基因组的3'端。我们展示了在人类感染过程中表达的Spike基因上游(位于orf1b的nsp16编码区)和典型包膜基因TRS的上游,这两个基因在多个谱系中都是趋同进化的。最常见的neo-TRS位于核衣壳基因的编码区,并且几乎存在于所有来自B.1.1谱系的病毒中,包括相关的Alpha、Gamma、Omicron及其后代的变体。在这里,我们证明了这种TRS导致一种新的亚基因组mRNA的表达,该mRNA编码核衣壳的c端截短部分,核衣壳是I型干扰素产生的拮抗剂,有助于病毒在感染期间的适应性。我们观察到,当核衣壳编码序列发生突变时,与单独切除TRS时相比,表型不同。我们的研究结果表明,除了氨基酸水平外,SARS-CoV-2在功能RNA水平上也发生了进化变化。
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 去求助
来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
期刊最新文献
Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants. Emergence of SARS-CoV-2 subgenomic RNAs that enhance viral fitness and immune evasion. Language-specific neural dynamics extend syntax into the time domain. Persistently increased post-stress activity of paraventricular thalamic neurons is essential for the emergence of stress-induced alterations in behaviour. Viral and immune dynamics of genital human papillomavirus infections in young women with high temporal resolution.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1