Molecular epidemiology analysis of early variants of SARS-CoV-2 reveals the potential impact of mutations P504L and Y541C (NSP13) in the clinical COVID-19 outcomes.
Molecular epidemiology analysis of early variants of SARS-CoV-2 reveals the potential impact of mutations P504L and Y541C (NSP13) in the clinical COVID-19 outcomes.
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DOI：
10.1016/j.meegid.2021.104831
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Wu P
中科院分区：
文献类型：
--
作者：
Cao C;He L;Tian Y;Qin Y;Sun H;Ding W;Gui L;Wu P
严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）以惊人的速度在全球范围内引起大流行，全面分析早期SARS-CoV-2毒株的突变和进化有助于发现和预防这种病毒。在这里，我们探索了来自42个国家的1962个高质量的早期SARS-CoV-2菌株基因组，这些基因组在2020年4月之前获得。随后确定了SARS-CoV-2菌株遗传变异随时间和国家的变化趋势。此外，还进行了病毒基因型定位和系统发育分析，以确定SARS-CoV-2的变异特征。结果表明，ORF1ab涉及57.89%的遗传变异，其中大部分（68.85%）为非同义变异。单倍型图谱和系统发育树分析显示，ORF1ab （p.5828P > L和p.5865Y > C，以及NSP13: P504L和NSP13: Y541C）的氨基酸变异是该进化支的重要特征。此外，这些变异在美国的聚集性（P = 2.92E-66, 95%）高于澳大利亚和加拿大，尤其是在华盛顿州（P = 1.56E-23, 77.65%）。进一步分析表明，变异的报告日期与美国感染增加的日期以及恢复和死亡率变化的日期有关。更重要的是，华盛顿州的致死率较高（4.13%），结果较差（致死率P = 4.12E-21，死亡病例和康复病例P = 3.64E-29），而其他州含有少量具有此类变异的菌株。通过序列比对，我们发现504和541位点的变异对NSP13具有功能影响。在这项研究中，我们全面分析了SARS-CoV-2的遗传变异，深入了解了ORF1ab的氨基酸变异和COVID-19的结局。
Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global pandemic with alarming speed, comprehensively analyzing the mutation and evolution of early SARS-CoV-2 strains contributes to detect and prevent such virus. Here, we explored 1962 high-quality genomes of early SARS-CoV-2 strains obtained from 42 countries before April 2020. The changing trends of genetic variations in SARS-CoV-2 strains over time and country were subsequently identified. In addition, viral genotype mapping and phylogenetic analysis were performed to identify the variation features of SARS-CoV-2. Results showed that 57.89% of genetic variations involved in ORF1ab, most of which (68.85%) were nonsynonymous. Haplotype maps and phylogenetic tree analysis showed that amino acid variations in ORF1ab (p.5828P > L and p.5865Y > C, also NSP13: P504L and NSP13: Y541C) were the important characteristics of such clade. Furthermore, these variants showed more significant aggregation in the United States (P = 2.92E-66, 95%) than in Australia or Canada, especially in strains from Washington State (P = 1.56E-23, 77.65%). Further analysis demonstrated that the report date of the variants was associated with the date of increased infections and the date of recovery and fatality rate change in the United States. More importantly, the fatality rate in Washington State was higher (4.13%) and showed poorer outcomes (P = 4.12E-21 in fatality rate, P = 3.64E-29 in death and recovered cases) than found in other states containing a small proportion of strains with such variants. Using sequence alignment, we found that variations at the 504 and 541 sites had functional effects on NSP13. In this study, we comprehensively analyzed genetic variations in SARS-CoV-2, gaining insights into amino acid variations in ORF1ab and COVID-19 outcomes.
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