Intra-host mutation rate of acute SARS-CoV-2 infection during the initial pandemic wave
Intra-host mutation rate of acute SARS-CoV-2 infection during the initial pandemic wave
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DOI：
10.1007/s11262-023-02011-0
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发表时间：
2023-06
期刊：
影响因子：
1.6
通讯作者：
Kim El-Haddad;T. M. Adhikari;Zheng Jin Tu;Yu-Wei Cheng;Xiaoyi Leng;Xiangyi Zhang;D. Rhoads;J. Ko;S. Worley;Jing Li;B. Rubin;Frank P Esper
中科院分区：
文献类型：
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作者：
Kim El-Haddad;T. M. Adhikari;Zheng Jin Tu;Yu-Wei Cheng;Xiaoyi Leng;Xiangyi Zhang;D. Rhoads;J. Ko;S. Worley;Jing Li;B. Rubin;Frank P Esper
SARS-CoV-2突变通过NSP-14编码的校对功能被最小化。大多数SARS-CoV-2突变率的估计值来自基于群体的序列数据。通过分析特定人群中宿主内病毒突变率，我们可能会增强对SARS-CoV-2进化的理解。在配对样本之间进行病毒基因组分析，并在等位基因频率（AF）≥ 0.25、≥ 0.5和≥ 0.75时定量突变。采用F81和JC 69进化模型确定突变率，并比较NSP-14中有（ΔNSP-14）和无（wtNSP-14）非同义突变的分离株以及患者合并症。分析了40个配对样本，中位间隔为13天[IQR 8.5-20]。在AF ≥ 0.25、≥ 0.5、≥ 0.75时，通过F81建模估计的突变率分别为93.6（95%CI 90.8-96.4）、40.7（95%CI 38.9-42.6）和34.7（95%CI 33.0-36.4）个置换/基因组/年。AF ≥ 0.25时ΔNSP-14突变率显著高于wtNSP-14。有免疫共病的患者在所有等位基因频率上的突变率都较高。宿主内SARS-CoV-2突变率大大高于通过人群分析报告的突变率。在低AF时，NSP-14改变的病毒株突变率加快。免疫抑制患者在所有AF时突变率升高。了解宿主内病毒演变将有助于当前和未来的大流行建模。
SARS-CoV-2 mutation is minimized through a proofreading function encoded byNSP-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.