Kim El-Haddad, Thamali M Adhikari, Zheng Jin Tu, Yu-Wei Cheng, Xiaoyi Leng, Xiangyi Zhang, Daniel Rhoads, Jennifer S Ko, Sarah Worley, Jing Li, Brian P Rubin, Frank P Esper
{"title":"疫情初期急性严重急性呼吸系统综合征冠状病毒2型感染的宿主内突变率。","authors":"Kim El-Haddad, Thamali M Adhikari, Zheng Jin Tu, Yu-Wei Cheng, Xiaoyi Leng, Xiangyi Zhang, Daniel Rhoads, Jennifer S Ko, Sarah Worley, Jing Li, Brian P Rubin, Frank P Esper","doi":"10.1007/s11262-023-02011-0","DOIUrl":null,"url":null,"abstract":"<p><p>SARS-CoV-2 mutation is minimized through a proofreading function encoded by NSP-14. Most estimates of the SARS-CoV-2 mutation rate are derived from population based sequence data. Our understanding of SARS-CoV-2 evolution might be enhanced through analysis of intra-host viral mutation rates in specific populations. Viral genome analysis was performed between paired samples and mutations quantified at allele frequencies (AF) ≥ 0.25, ≥ 0.5 and ≥ 0.75. Mutation rate was determined employing F81 and JC69 evolution models and compared between isolates with (ΔNSP-14) and without (wtNSP-14) non-synonymous mutations in NSP-14 and by patient comorbidity. Forty paired samples with median interval of 13 days [IQR 8.5-20] were analyzed. The estimated mutation rate by F81 modeling was 93.6 (95%CI 90.8-96.4], 40.7 (95%CI 38.9-42.6) and 34.7 (95%CI 33.0-36.4) substitutions/genome/year at AF ≥ 0.25, ≥ 0.5, ≥ 0.75 respectively. Mutation rate in ΔNSP-14 were significantly elevated at AF ≥ 0.25 vs wtNSP-14. Patients with immune comorbidities had higher mutation rate at all allele frequencies. Intra-host SARS-CoV-2 mutation rates are substantially higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated mutation rate at low AF. Immunosuppressed patients have elevated mutation rate at all AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling.</p>","PeriodicalId":51212,"journal":{"name":"Virus Genes","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Intra-host mutation rate of acute SARS-CoV-2 infection during the initial pandemic wave.\",\"authors\":\"Kim El-Haddad, Thamali M Adhikari, Zheng Jin Tu, Yu-Wei Cheng, Xiaoyi Leng, Xiangyi Zhang, Daniel Rhoads, Jennifer S Ko, Sarah Worley, Jing Li, Brian P Rubin, Frank P Esper\",\"doi\":\"10.1007/s11262-023-02011-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>SARS-CoV-2 mutation is minimized through a proofreading function encoded by NSP-14. Most estimates of the SARS-CoV-2 mutation rate are derived from population based sequence data. Our understanding of SARS-CoV-2 evolution might be enhanced through analysis of intra-host viral mutation rates in specific populations. Viral genome analysis was performed between paired samples and mutations quantified at allele frequencies (AF) ≥ 0.25, ≥ 0.5 and ≥ 0.75. Mutation rate was determined employing F81 and JC69 evolution models and compared between isolates with (ΔNSP-14) and without (wtNSP-14) non-synonymous mutations in NSP-14 and by patient comorbidity. Forty paired samples with median interval of 13 days [IQR 8.5-20] were analyzed. The estimated mutation rate by F81 modeling was 93.6 (95%CI 90.8-96.4], 40.7 (95%CI 38.9-42.6) and 34.7 (95%CI 33.0-36.4) substitutions/genome/year at AF ≥ 0.25, ≥ 0.5, ≥ 0.75 respectively. Mutation rate in ΔNSP-14 were significantly elevated at AF ≥ 0.25 vs wtNSP-14. Patients with immune comorbidities had higher mutation rate at all allele frequencies. Intra-host SARS-CoV-2 mutation rates are substantially higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated mutation rate at low AF. Immunosuppressed patients have elevated mutation rate at all AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling.</p>\",\"PeriodicalId\":51212,\"journal\":{\"name\":\"Virus Genes\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Virus Genes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11262-023-02011-0\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/6/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virus Genes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11262-023-02011-0","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/13 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Intra-host mutation rate of acute SARS-CoV-2 infection during the initial pandemic wave.
SARS-CoV-2 mutation is minimized through a proofreading function encoded by NSP-14. Most estimates of the SARS-CoV-2 mutation rate are derived from population based sequence data. Our understanding of SARS-CoV-2 evolution might be enhanced through analysis of intra-host viral mutation rates in specific populations. Viral genome analysis was performed between paired samples and mutations quantified at allele frequencies (AF) ≥ 0.25, ≥ 0.5 and ≥ 0.75. Mutation rate was determined employing F81 and JC69 evolution models and compared between isolates with (ΔNSP-14) and without (wtNSP-14) non-synonymous mutations in NSP-14 and by patient comorbidity. Forty paired samples with median interval of 13 days [IQR 8.5-20] were analyzed. The estimated mutation rate by F81 modeling was 93.6 (95%CI 90.8-96.4], 40.7 (95%CI 38.9-42.6) and 34.7 (95%CI 33.0-36.4) substitutions/genome/year at AF ≥ 0.25, ≥ 0.5, ≥ 0.75 respectively. Mutation rate in ΔNSP-14 were significantly elevated at AF ≥ 0.25 vs wtNSP-14. Patients with immune comorbidities had higher mutation rate at all allele frequencies. Intra-host SARS-CoV-2 mutation rates are substantially higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated mutation rate at low AF. Immunosuppressed patients have elevated mutation rate at all AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling.
期刊介绍:
Viruses are convenient models for the elucidation of life processes. The study of viruses is again on the cutting edge of biological sciences: systems biology, genomics, proteomics, metagenomics, using the newest most powerful tools.
Huge amounts of new details on virus interactions with the cell, other pathogens and the hosts – animal (including human), insect, fungal, plant, bacterial, and archaeal - and their role in infection and disease are forthcoming in perplexing details requiring analysis and comments.
Virus Genes is dedicated to the publication of studies on the structure and function of viruses and their genes, the molecular and systems interactions with the host and all applications derived thereof, providing a forum for the analysis of data and discussion of its implications, and the development of new hypotheses.