2. Academic Validation
  3. Spike mutation D614G alters SARS-CoV-2 fitness

Spike mutation D614G alters SARS-CoV-2 fitness

  • Nature. 2021 Apr;592(7852):116-121. doi: 10.1038/s41586-020-2895-3.
Jessica A Plante  # 1 2 3,  Yang Liu  # 4,  Jianying Liu  # 2 3,  Hongjie Xia 4,  Bryan A Johnson 2,  Kumari G Lokugamage 3,  Xianwen Zhang 4,  Antonio E Muruato 2 3,  Jing Zou 4,  Camila R Fontes-Garfias 4,  Divya Mirchandani 1 2 3,  Dionna Scharton 1 2 3,  John P Bilello 5,  Zhiqiang Ku 6,  Zhiqiang An 6,  Birte Kalveram 7,  Alexander N Freiberg 2 7 8 9,  Vineet D Menachery 2 3,  Xuping Xie 10,  Kenneth S Plante 11 12 13,  Scott C Weaver 14 15 16 17 18 19 20,  Pei-Yong Shi 21 22 23 24 25 26
Affiliations

Affiliations

  • 1 World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.
  • 2 Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
  • 3 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
  • 4 Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
  • 5 Gilead Sciences, Foster City, CA, USA.
  • 6 Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
  • 7 Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  • 8 Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA.
  • 9 Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA.
  • 10 Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA. xuxie@utmb.edu.
  • 11 World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA. ksplante@utmb.edu.
  • 12 Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA. ksplante@utmb.edu.
  • 13 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA. ksplante@utmb.edu.
  • 14 World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA. sweaver@utmb.edu.
  • 15 Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA. sweaver@utmb.edu.
  • 16 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA. sweaver@utmb.edu.
  • 17 Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA. sweaver@utmb.edu.
  • 18 Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA. sweaver@utmb.edu.
  • 19 Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA. sweaver@utmb.edu.
  • 20 Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA. sweaver@utmb.edu.
  • 21 Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA. peshi@utmb.edu.
  • 22 Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA. peshi@utmb.edu.
  • 23 Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA. peshi@utmb.edu.
  • 24 Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA. peshi@utmb.edu.
  • 25 Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA. peshi@utmb.edu.
  • 26 Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA. peshi@utmb.edu.
  • # Contributed equally.
PMID: 33106671 DOI: 10.1038/s41586-020-2895-3
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.

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