Antigenic Evolution on a Global Scale Reveals the Potential Natural Selection of Severe Acute Respiratory Syndrome-Coronavirus 2 by Pre-existing Cross-Reactive T-Cell Immunity.
Antigenic Evolution on a Global Scale Reveals the Potential Natural Selection of Severe Acute Respiratory Syndrome-Coronavirus 2 by Pre-existing Cross-Reactive T-Cell Immunity.
复制标题
全球范围内的抗原进化揭示了通过预先存在的交叉反应性 T 细胞免疫对严重急性呼吸系统综合症冠状病毒 2 进行潜在的自然选择
DOI：
10.3389/fmicb.2021.599562
复制
发表时间：
2021
影响因子：
5.2
通讯作者：
Qiu T
中科院分区：
文献类型：
--
作者：
Zhang C;Jin X;Chen X;Qiu L;Leng Q;Qiu T
严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）在全球范围内的社区传播过程中，其变异模式不断发生变化。然而，突变模式变化的原因仍不清楚。因此，在这项研究中，我们对来自13，432株SARS-CoV-2菌株的超过3亿个肽进行了全面分析，这些菌株含有4，420个氨基酸突变，以分析宿主免疫系统的潜在选择压力，并揭示循环SARS-CoV-2分离株中突变的驱动因素。结果表明，非结构蛋白ORF 1ab和结构蛋白Spike最易发生突变。此外，SARS-CoV-2和季节性人类冠状病毒之间的交叉反应性T细胞表位的突变可能有助于SARS-CoV-2在长期和大规模社区传播下逃避细胞免疫。此外，通过同源性建模和蛋白质对接，刺突蛋白的突变可能增强SARS-CoV-2入侵宿主细胞和逃避抗体介导的B细胞免疫的能力。我们的研究为SARS-CoV-2在自然选择下的潜在突变模式提供了见解，提高了我们对病毒进化的理解，并为潜在的疫苗设计建立了重要指导。
The mutation pattern of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has changed constantly during worldwide community transmission of this virus. However, the reasons for the changes in mutation patterns are still unclear. Accordingly, in this study, we present a comprehensive analysis of over 300 million peptides derived from 13,432 SARS-CoV-2 strains harboring 4,420 amino acid mutations to analyze the potential selective pressure of the host immune system and reveal the driver of mutations in circulating SARS-CoV-2 isolates. The results showed that the nonstructural protein ORF1ab and the structural protein Spike were most susceptible to mutations. Furthermore, mutations in cross-reactive T-cell epitopes between SARS-CoV-2 and seasonal human coronavirus may help SARS-CoV-2 to escape cellular immunity under long-term and large-scale community transmission. Additionally, through homology modeling and protein docking, mutations in Spike protein may enhance the ability of SARS-CoV-2 to invade host cells and escape antibody-mediated B-cell immunity. Our research provided insights into the potential mutation patterns of SARS-CoV-2 under natural selection, improved our understanding of the evolution of the virus, and established important guidance for potential vaccine design.
登录
查看更多内容
影响因子：
5.2
作者：
Mercatelli, Daniele;Giorgi, Federico M.
通讯作者：
Giorgi, Federico M.
影响因子：
56.9
作者：
Kissler, Stephen M.;Tedijanto, Christine;Lipsitch, Marc
通讯作者：
Lipsitch, Marc
影响因子：
20.6
作者：
Tang, Xiaolu;Wu, Changcheng;Lu, Jian
通讯作者：
Lu, Jian
影响因子：
3.8
作者：
Setiawan, Laurentia C.;Gijsbers, Esther F.;Kootstra, Neeltje A.
通讯作者：
Kootstra, Neeltje A.
DOI：
10.1016/s0140-6736(20)32137-1
发表时间：
2020-11-14
期刊：
Lancet (London, England)
影响因子：
--
作者：
Poland GA;Ovsyannikova IG;Kennedy RB
通讯作者：
Kennedy RB