Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape.
Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape.
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DOI：
10.1126/science.abf6950
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发表时间：
2021-03-12
期刊：
影响因子：
--
通讯作者：
Duprex WP
中科院分区：
文献类型：
--
作者：
McCarthy KR;Rennick LJ;Nambulli S;Robinson-McCarthy LR;Bain WG;Haidar G;Duprex WP
流感病毒逃避先前感染引发的免疫，这解释了流感大流行的反复发生。与流感病毒中易于出错的RNA依赖性RNA聚合酶不同，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）和相关病毒含有具有校对活性的聚合酶。然而，校对不能纠正缺失，在长期持续感染期间，这可能导致病毒的产生，显示整个氨基酸及其形成的结构的改变。McCarthy等人鉴定了由SARS-CoV-2刺突蛋白中四个抗原位点的普遍和复发性缺失定义的进化特征。缺失变体显示具有改变的抗原性的病毒的人与人之间的传播。在持续感染的个体中独立出现的SARS-CoV-2基因组缺失显示出反复和趋同的进化。人畜共患大流行病，如由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的大流行病，可以在动物病毒溢出后进入高度易感的人群。这些病毒的后代已经适应了人类宿主，并进化为逃避免疫压力。冠状病毒获得替换比其他RNA病毒更慢。在刺突糖蛋白中，我们发现复发性缺失克服了这种缓慢的取代速率。缺失变异出现在不同的遗传和地理背景中，有效地传播，并存在于新的谱系中，包括目前全球关注的谱系。它们经常占据重复缺失区（RDR），其映射到定义的抗体表位。RDR中的缺失赋予对中和抗体的抗性。通过改变氨基酸的延伸，缺失似乎加速了SARS-CoV-2抗原的进化，更普遍地说，可能会驱动适应性进化。
Influenza viruses evade immunity initiated by previous infection, which explains recurrent influenza pandemics. Unlike the error-prone RNA-dependent RNA polymerase of influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related viruses contain polymerases with proofreading activity. However, proofreading cannot correct deletions, which during a long-term persistent infection could result in the generation of viruses showing alteration of entire stretches of amino acids and the structures they form. McCarthy et al. identified an evolutionary signature defined by prevalent and recurrent deletions in the spike protein of SARS-CoV-2 at four antigenic sites. Deletion variants show human-to-human transmission of viruses with altered antigenicity. Science, this issue p. 1139 SARS-CoV-2 genome deletions that arise independently in persistently infected individuals show recurrent and convergent evolution. Zoonotic pandemics, such as that caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can follow the spillover of animal viruses into highly susceptible human populations. The descendants of these viruses have adapted to the human host and evolved to evade immune pressure. Coronaviruses acquire substitutions more slowly than other RNA viruses. In the spike glycoprotein, we found that recurrent deletions overcome this slow substitution rate. Deletion variants arise in diverse genetic and geographic backgrounds, transmit efficiently, and are present in novel lineages, including those of current global concern. They frequently occupy recurrent deletion regions (RDRs), which map to defined antibody epitopes. Deletions in RDRs confer resistance to neutralizing antibodies. By altering stretches of amino acids, deletions appear to accelerate SARS-CoV-2 antigenic evolution and may, more generally, drive adaptive evolution.
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影响因子：
10.7
作者：
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通讯作者：
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DOI：
10.1099/jgv.0.001481
发表时间：
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期刊：
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影响因子：
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发表时间：
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期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
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