Spike mutation D614G alters SARS-CoV-2 fitness

Jessica A. Plante, Yang Liu, Jianying Liu, Hongjie Xia, Bryan A. Johnson, Kumari G. Lokugamage, Xianwen Zhang, Antonio E. Muruato, Jing Zou, Camila R. Fontes-Garfias, Divya Mirchandani, Dionna Scharton, John P. Bilello, Zhiqiang Ku, Zhiqiang An, Birte Kalveram, Alexander N. Freiberg, Vineet D. Menachery, Xuping Xie (), Kenneth S. Plante (), Scott C. Weaver () and Pei-Yong Shi ()
Additional contact information
Jessica A. Plante: University of Texas Medical Branch
Yang Liu: University of Texas Medical Branch
Jianying Liu: University of Texas Medical Branch
Hongjie Xia: University of Texas Medical Branch
Bryan A. Johnson: University of Texas Medical Branch
Kumari G. Lokugamage: University of Texas Medical Branch
Xianwen Zhang: University of Texas Medical Branch
Antonio E. Muruato: University of Texas Medical Branch
Jing Zou: University of Texas Medical Branch
Camila R. Fontes-Garfias: University of Texas Medical Branch
Divya Mirchandani: University of Texas Medical Branch
Dionna Scharton: University of Texas Medical Branch
John P. Bilello: Gilead Sciences
Zhiqiang Ku: University of Texas Health Science Center at Houston
Zhiqiang An: University of Texas Health Science Center at Houston
Birte Kalveram: University of Texas Medical Branch
Alexander N. Freiberg: University of Texas Medical Branch
Vineet D. Menachery: University of Texas Medical Branch
Xuping Xie: University of Texas Medical Branch
Kenneth S. Plante: University of Texas Medical Branch
Scott C. Weaver: University of Texas Medical Branch
Pei-Yong Shi: University of Texas Medical Branch

Nature, 2021, vol. 592, issue 7852, 116-121

Abstract: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein substitution D614G became dominant during the coronavirus disease 2019 (COVID-19) pandemic1,2. 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.

Date: 2021
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DOI: 10.1038/s41586-020-2895-3

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