SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo

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  • Hou, Yixuan J.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Chiba, Shiho
    • Other Affiliation: University of Wisconsin, Madison
  • Halfmann, Peter
    • Other Affiliation: University of Wisconsin, Madison
  • Ehre, Camille
    • Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
  • Kuroda, Makoto
    • Other Affiliation: University of Wisconsin, Madison
  • Dinnon, Kenneth H.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Leist, Sarah R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Schäfer, Alexandra
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Nakajima, Noriko
    • Other Affiliation: National Institute of Infectious Diseases, Tokyo
  • Takahashi, Kenta
    • Other Affiliation: National Institute of Infectious Diseases, Tokyo
  • Lee, Rhianna E.
    • Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
  • Mascenik, Teresa M.
    • Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
  • Graham, Rachel
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Edwards, Caitlin E.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Tse, Longping V.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Okuda, Kenichi
    • Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
  • Markmann, Alena J.
    • Affiliation: School of Medicine, Department of Medicine
  • Bartelt, Luther
    • Affiliation: School of Medicine, Department of Medicine
  • de Silva, Aravinda
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Margolis, David M.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Boucher, Richard C.
    • Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
  • Randell, Scott H.
    • Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
  • Suzuki, Tadaki
    • Other Affiliation: National Institute of Infectious Diseases, Tokyo
  • Gralinski, Lisa E.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Kawaoka, Yoshihiro
    • Other Affiliation: University of Wisconsin, Madison
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • The spike D614G substitution is prevalent in global SARS-CoV-2 strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells, but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models.
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  • Article
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  • In Copyright
License
  • Attribution 3.0 United States
Journal title
  • Science
Language
  • English
ISSN
  • 0036-8075, 1095-9203

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