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SARS-CoV-2 刺突糖蛋白的反复缺失可导致抗体逃逸。

Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape.

机构信息

Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

出版信息

Science. 2021 Mar 12;371(6534):1139-1142. doi: 10.1126/science.abf6950. Epub 2021 Feb 3.

Abstract

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.

摘要

人畜共患大流行,例如由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的大流行,可能是由于动物病毒溢出到高度易感的人群中引起的。这些病毒的后代已经适应了人类宿主,并进化以逃避免疫压力。冠状病毒比其他 RNA 病毒获得替换的速度更慢。在刺突糖蛋白中,我们发现反复发生的缺失克服了这种缓慢的替换速度。缺失变体出现在不同的遗传和地理背景中,能够有效地传播,并存在于新的谱系中,包括目前全球关注的谱系。它们经常出现在反复出现的缺失区域(RDR),这些区域映射到定义的抗体表位。RDR 中的缺失赋予了对中和抗体的抗性。通过改变氨基酸的延伸,缺失似乎加速了 SARS-CoV-2 的抗原进化,并且可能更普遍地推动了适应性进化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8416/7971772/cee8f0351718/371_1139_F1.jpg

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