Antigenic variation of SARS-CoV-2 in response to immune pressure.
Antigenic variation of SARS-CoV-2 in response to immune pressure.
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DOI：
10.1111/mec.15730
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发表时间：
2020-12-02
影响因子：
4.9
通讯作者：
Sironi M
中科院分区：
文献类型：
--
作者：
Forni D;Cagliani R;Pontremoli C;Mozzi A;Pozzoli U;Clerici M;Sironi M
对与SARS-CoV-2最密切相关的蝙蝠病毒的分析表明，该病毒可能需要有限的适应才能在人类中传播。尽管如此，自从SARS-CoV-2被引入人类群体以来，它必须受到人类免疫系统施加的选择压力。我们利用了大量高质量的SARS-CoV-2基因组的可用性，以及经验证的表位预测，以表明刺突糖蛋白（S）和核衣壳蛋白（N）中的B细胞表位比非表位位置具有更高的多样性。其他人类冠状病毒和蝙蝠中的肉瘤病毒样本也得到了类似的结果。相反，在SARS-CoV-2人群中，CD 4+和CD 8 + T细胞的表位并不比非表位位置更易变。相反，对于一些最具免疫原性的蛋白质（S、N、ORF 8和ORF 3a），观察到表位变异性的显著降低。在较长的进化时间框架的分析表明，这种影响是不是由于差分约束。这些数据表明，SARS-CoV-2进化为逃避宿主的体液免疫反应，而T细胞的识别并没有被病毒主动避免。然而，我们也发现了普通感冒冠状病毒T细胞表位多样性较低的趋势，表明表位保守性本身与疾病严重程度没有直接联系。我们认为，保守性有助于维持引起耐受性T细胞反应或诱导具有调节活性的T细胞的表位。
Analysis of the bat viruses most closely related to SARS‐CoV‐2 indicated that the virus probably required limited adaptation to spread in humans. Nonetheless, since its introduction in human populations, SARS‐CoV‐2 must have been subject to the selective pressure imposed by the human immune system. We exploited the availability of a large number of high‐quality SARS‐CoV‐2 genomes, as well as of validated epitope predictions, to show that B cell epitopes in the spike glycoprotein (S) and in the nucleocapsid protein (N) have higher diversity than nonepitope positions. Similar results were obtained for other human coronaviruses and for sarbecoviruses sampled in bats. Conversely, in the SARS‐CoV‐2 population, epitopes for CD4+ and CD8+ T cells were not more variable than nonepitope positions. A significant reduction in epitope variability was instead observed for some of the most immunogenic proteins (S, N, ORF8 and ORF3a). Analysis over longer evolutionary time frames indicated that this effect is not due to differential constraints. These data indicate that SARS‐CoV‐2 evolves to elude the host humoral immune response, whereas recognition by T cells is not actively avoided by the virus. However, we also found a trend of lower diversity of T cell epitopes for common cold coronaviruses, indicating that epitope conservation per se is not directly linked to disease severity. We suggest that conservation serves to maintain epitopes that elicit tolerizing T cell responses or induce T cells with regulatory activity.
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影响因子：
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作者：
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作者：
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通讯作者：
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3.7
作者：
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通讯作者：
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