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新冠疫情期间严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白的表型演变

Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic.

作者信息

Furnon Wilhelm, Cowton Vanessa M, De Lorenzo Giuditta, Orton Richard, Herder Vanessa, Cantoni Diego, Ilia Georgios, Mendonca Diogo Correa, Kerr Karen, Allan Jay, Upfold Nicole, Meehan Gavin R, Bakshi Siddharth, Das Udeet Ranjan, Molina Arias Sergi, McElwee Marion, Little Sarah, Logan Nicola, Kwok Kirsty, Smollett Katherine, Willett Brian J, Da Silva Filipe Ana, Robertson David L, Grove Joe, Patel Arvind H, Palmarini Massimo

机构信息

MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.

CVR-CRUSH, MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.

出版信息

Nat Microbiol. 2025 Jan;10(1):77-93. doi: 10.1038/s41564-024-01878-5. Epub 2025 Jan 3.

DOI:10.1038/s41564-024-01878-5
PMID:39753670
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11726466/
Abstract

SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging to comprehensively compare the many spikes that emerged during the pandemic in a single experimental platform. Here we generated a panel of recombinant viruses carrying different spike proteins from 27 variants circulating between 2020 and 2024 in the same genomic background. We then assessed several of their phenotypic traits both in vitro and in vivo. We found distinct phenotypic trajectories of spike among and between variants circulating before and after the emergence of Omicron variants. Spike of post-Omicron variants maintained enhanced tropism for the nasal epithelium and large airways but displayed, over time, several phenotypic traits typical of the pre-Omicron variants. Hence, spike with phenotypic features of both pre- and post-Omicron variants may continue to emerge in the future.

摘要

严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体主要由其刺突蛋白的突变所定义。因此，了解刺突蛋白的进化轨迹如何影响病毒表型至关重要。到目前为止，在单一实验平台上全面比较大流行期间出现的众多刺突蛋白一直具有挑战性。在这里，我们构建了一组重组病毒，它们在相同的基因组背景下携带2020年至2024年间流行的27种变体的不同刺突蛋白。然后，我们在体外和体内评估了它们的几种表型特征。我们发现在奥密克戎变体出现之前和之后流行的变体之间以及变体内部，刺突蛋白具有不同的表型轨迹。奥密克戎变体出现后的刺突蛋白对鼻上皮和大气道保持增强的嗜性，但随着时间的推移，表现出几种典型的奥密克戎变体出现前的表型特征。因此，具有奥密克戎变体出现前后表型特征的刺突蛋白未来可能会继续出现。

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