SARS-CoV-2 Alpha, Beta, and Delta variants display enhanced Spike-mediated syncytia formation.
SARS-CoV-2 Alpha, Beta, and Delta variants display enhanced Spike-mediated syncytia formation.
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SARS-CoV-2 Alpha、Beta 和 Delta 变体表现出增强的刺突介导的合胞体形成。
DOI：
10.15252/embj.2021108944
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发表时间：
2021-12-15
期刊：
影响因子：
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通讯作者：
Schwartz O
中科院分区：
文献类型：
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作者：
Rajah MM;Hubert M;Bishop E;Saunders N;Robinot R;Grzelak L;Planas D;Dufloo J;Gellenoncourt S;Bongers A;Zivaljic M;Planchais C;Guivel-Benhassine F;Porrot F;Mouquet H;Chakrabarti LA;Buchrieser J;Schwartz O
重症新冠肺炎的特征是肺部异常，包括合体肺泡细胞的存在。当感染细胞表面表达的SARS-CoV-2刺突蛋白与邻近细胞上的ACE2受体相互作用时，合胞体就形成了。穗状突变体蛋白的合胞体形成潜力仍然没有得到很好的描述。在这里，我们首先评估了阿尔法(B.1.1.7)和贝塔(B.1.351)在细胞培养中的传播和融合，并与祖先的D614G株进行了比较。Alpha和Beta在Vero、Caco-2、Calu-3和原代呼吸道细胞中复制的方式与D614G相似。然而，阿尔法和贝塔形成了更大、更多的合胞体。与D614G相比，变异的Spike蛋白表现出更高的ACE2亲和力。干扰素诱导的跨膜蛋白(IFITM)同样抑制了α、β和D614G的融合。在Alpha和Beta棘突中存在的个别突变改变了融合能力，与ACE2结合或被单抗识别。我们进一步表明，Delta Spike也比D614G触发了更快的融合。因此，SARS-CoV-2新出现的变种表现出增强的合胞体形成。新出现的SARS-CoV-2变异体表达的刺突蛋白突变不同地影响宿主细胞与细胞的融合、ACE2受体结合和抗体逃逸。
Severe COVID‐19 is characterized by lung abnormalities, including the presence of syncytial pneumocytes. Syncytia form when SARS‐CoV‐2 spike protein expressed on the surface of infected cells interacts with the ACE2 receptor on neighboring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha (B.1.1.7) and Beta (B.1.351) spread and fusion in cell cultures, compared with the ancestral D614G strain. Alpha and Beta replicated similarly to D614G strain in Vero, Caco‐2, Calu‐3, and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Variant spike proteins displayed higher ACE2 affinity compared with D614G. Alpha, Beta, and D614G fusion was similarly inhibited by interferon‐induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes modified fusogenicity, binding to ACE2 or recognition by monoclonal antibodies. We further show that Delta spike also triggers faster fusion relative to D614G. Thus, SARS‐CoV‐2 emerging variants display enhanced syncytia formation. Spike protein mutations expressed by emerging SARS‐CoV‐2 variants‐of‐concern differentially affect host cell‐to‐cell fusion, ACE2 receptor binding, and antibody escape.