The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein substitution D614G became dominant during the coronavirus disease 2019 (COVID-19) pandemic 1 , 2 . However, the effect of this variant on viral spread and vaccine efficacy remains to be defined. Here we engineered the spike D614G substitution in the USA-WA1/2020 SARS-CoV-2 strain, and found that it enhances viral replication in human lung epithelial cells and primary human airway tissues by increasing the infectivity and stability of virions. Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission. Sera from hamsters infected with D614 virus exhibit modestly higher neutralization titres against G614 virus than against D614 virus, suggesting that the mutation is unlikely to reduce the ability of vaccines in clinical trials to protect against COVID-19, and that therapeutic antibodies should be tested against the circulating G614 virus. Together with clinical findings, our work underscores the importance of this variant in viral spread and its implications for vaccine efficacy and antibody therapy. The SARS-CoV-2 variant expressing spike(D641G) shows increased infectivity in human lung epithelial cells and in hamster and primary human upper airway tissues, but is more susceptible to neutralization by antibodies raised against SARS-CoV-2.

中文翻译：

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尖峰突变 D614G 改变 SARS-CoV-2 的适应性


严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 刺突蛋白替代 D614G 在 2019 年冠状病毒病 (COVID-19) 大流行期间占据主导地位 1 , 2 。然而，这种变体对病毒传播和疫苗功效的影响仍有待确定。在这里，我们在 USA-WA1/2020 SARS-CoV-2 毒株中设计了刺突 D614G 取代，发现它通过增加病毒粒子的感染性和稳定性来增强病毒在人肺上皮细胞和初级人气道组织中的复制。感染了表达刺突 (D614G)（G614 病毒）的 SARS-CoV-2 的仓鼠在鼻腔冲洗液和气管中产生了更高的感染滴度，但在肺部中却没有，这支持了临床证据，表明该突变增强了仓鼠上呼吸道的病毒载量。 COVID-19 患者，可能会增加传播。感染 D614 病毒的仓鼠血清表现出针对 G614 病毒的中和滴度略高于针对 D614 病毒的中和滴度，这表明该突变不太可能降低临床试验中疫苗预防 COVID-19 的能力，并且应测试治疗性抗体流行的 G614 病毒。结合临床发现，我们的工作强调了这种变异在病毒传播中的重要性及其对疫苗功效和抗体治疗的影响。表达 SARS-CoV-2 变体的刺突 (D641G) 在人肺上皮细胞、仓鼠和原代人上呼吸道组织中显示出感染性增加，但更容易被针对 SARS-CoV-2 的抗体中和。