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The human microbiota is a beneficial reservoir for SARS-CoV-2 mutations

文献类型：期刊论文

作者Cao, Birong2,3,4; Wang, Xiaoxi3,4; Yin, Wanchao1,3,4; Gao, Zhaobing1,3,4; Xia, Bingqing3,4
刊名MBIO
出版日期2024-03-26
页码15
关键词human microbiota SARS-CoV-2 advantageous mutations evolution
ISSN号2150-7511
DOI10.1128/mbio.03187-23
通讯作者Gao, Zhaobing(zbgao@simm.ac.cn) ; Xia, Bingqing(xiabingqing@simm.ac.cn)
英文摘要Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations are rapidly emerging. In particular, beneficial mutations in the spike (S) protein, which can either make a person more infectious or enable immunological escape, are providing a significant obstacle to the prevention and treatment of pandemics. However, how the virus acquires a high number of beneficial mutations in a short time remains a mystery. We demonstrate here that variations of concern may be mutated due in part to the influence of the human microbiome. We searched the National Center for Biotechnology Information database for homologous fragments (HFs) after finding a mutation and the six neighboring amino acids in a viral mutation fragment. Among the approximate 8,000 HFs obtained, 61 mutations in S and other outer membrane proteins were found in bacteria, accounting for 62% of all mutation sources, which is 12-fold higher than the natural variable proportion. A significant proportion of these bacterial species-roughly 70%-come from the human microbiota, are mainly found in the lung or gut, and share a composition pattern with COVID-19 patients. Importantly, SARS-CoV-2 RNA-dependent RNA polymerase replicates corresponding bacterial mRNAs harboring mutations, producing chimeric RNAs. SARS-CoV-2 may collectively pick up mutations from the human microbiota that change the original virus's binding sites or antigenic determinants. Our study clarifies the evolving mutational mechanisms of SARS-CoV-2.IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations are rapidly emerging, in particular advantageous mutations in the spike (S) protein, which either increase transmissibility or lead to immune escape and are posing a major challenge to pandemic prevention and treatment. However, how the virus acquires a high number of advantageous mutations in a short time remains a mystery. Here, we provide evidence that the human microbiota is a reservoir of advantageous mutations and aids mutational evolution and host adaptation of SARS-CoV-2. Our findings demonstrate a conceptual breakthrough on the mutational evolution mechanisms of SARS-CoV-2 for human adaptation. SARS-CoV-2 may grab advantageous mutations from the widely existing microorganisms in the host, which is undoubtedly an "efficient" manner. Our study might open a new perspective to understand the evolution of virus mutation, which has enormous implications for comprehending the trajectory of the COVID-19 pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations are rapidly emerging, in particular advantageous mutations in the spike (S) protein, which either increase transmissibility or lead to immune escape and are posing a major challenge to pandemic prevention and treatment. However, how the virus acquires a high number of advantageous mutations in a short time remains a mystery. Here, we provide evidence that the human microbiota is a reservoir of advantageous mutations and aids mutational evolution and host adaptation of SARS-CoV-2. Our findings demonstrate a conceptual breakthrough on the mutational evolution mechanisms of SARS-CoV-2 for human adaptation. SARS-CoV-2 may grab advantageous mutations from the widely existing microorganisms in the host, which is undoubtedly an "efficient" manner. Our study might open a new perspective to understand the evolution of virus mutation, which has enormous implications for comprehending the trajectory of the COVID-19 pandemic.
WOS关键词COVID-19 ; VIRUSES ; RECOMBINATION ; MECHANISMS ; DYNAMICS ; IMPACT
资助项目STCSM | Science and Technology Innovation Plan Of Shanghai Science and Technology Commission
WOS研究方向Microbiology
语种英语
WOS记录号WOS:001192150000002
出版者AMER SOC MICROBIOLOGY
源URL[http://119.78.100.183/handle/2S10ELR8/310547]  
专题新药研究国家重点实验室
通讯作者Gao, Zhaobing; Xia, Bingqing
作者单位1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China
2.Guangdong Guangya High Sch, Guangzhou, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Cao, Birong,Wang, Xiaoxi,Yin, Wanchao,et al. The human microbiota is a beneficial reservoir for SARS-CoV-2 mutations[J]. MBIO,2024:15.
APA Cao, Birong,Wang, Xiaoxi,Yin, Wanchao,Gao, Zhaobing,&Xia, Bingqing.(2024).The human microbiota is a beneficial reservoir for SARS-CoV-2 mutations.MBIO,15.
MLA Cao, Birong,et al."The human microbiota is a beneficial reservoir for SARS-CoV-2 mutations".MBIO (2024):15.

入库方式： OAI收割

来源：上海药物研究所

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