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SARS-CoV-2突刺蛋白的D614G突变可增强病毒的复制和传播
2021-03-04 14:51

德国弗里德里希·勒夫勒研究院Martin Beer等研究人员合作发现,SARS-CoV-2突刺蛋白的D614G突变可增强病毒的复制和传播。这一研究成果于2021年2月26日在线发表在国际学术期刊《自然》上。

研究人员表示,SARS-CoV-2在人类中进化过程里出现了突刺(S)蛋白的D614G取代,并成为COVID-19大流行的主要流行变异体(S-614G)。但是,S-614G变异体的流行率提高是否代表改善人类复制和/或传播的适应性优势,或者仅仅是由于奠基者效应导致,尚不清楚。

研究人员生成了等基因的SARS-CoV-2变体,并证明S-614G变体具有(i)与人宿主细胞表面受体血管紧张素转化酶2(ACE2)的结合增强,(ii)在原代人类支气管和组织、鼻气道上皮培养物以及新型人类ACE2敲入小鼠模型中的复制增加,以及(iii)在SARS-CoV-2感染的仓鼠和雪貂模型中复制和传播能力显著提高。

总的来说,这些数据表明,尽管S-614G取代导致体外结合和复制的细微增加,但它在体内提供了真正的竞争优势,尤其是在传播瓶颈期间,这为S-614G的全球优势提供了解释。

附:英文原文

Title: SARS-CoV-2 spike D614G change enhances replication and transmission

Author: Bin Zhou, Tran Thi Nhu Thao, Donata Hoffmann, Adriano Taddeo, Nadine Ebert, Fabien Labroussaa, Anne Pohlmann, Jacqueline King, Silvio Steiner, Jenna N. Kelly, Jasmine Portmann, Nico Joel Halwe, Lorenz Ulrich, Bettina Salome Treb, Xiaoyu Fan, Bernd Hoffmann, Li Wang, Lisa Thomann, Xudong Lin, Hanspeter Stalder, Berta Pozzi, Simone de Brot, Nannan Jiang, Dan Cui, Jaber Hossain, Malania Wilson, Matthew Keller, Thomas J. Stark, John R. Barnes, Ronald Dijkman, Joerg Jores, Charaf Benarafa, David E. Wentworth, Volker Thiel, Martin Beer

Issue&Volume: 2021-02-26

Abstract: During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic1. However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human host cell surface receptor angiotensin-converting enzyme 2 (ACE2), (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro, it provides a real competitive advantage in vivo, particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

DOI: 10.1038/s41586-021-03361-1

Source: https://www.nature.com/articles/s41586-021-03361-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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