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SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo.
Hou, Yixuan J; Chiba, Shiho; Halfmann, Peter; Ehre, Camille; Kuroda, Makoto; Dinnon, Kenneth H; Leist, Sarah R; Schäfer, Alexandra; Nakajima, Noriko; Takahashi, Kenta; Lee, Rhianna E; Mascenik, Teresa M; Graham, Rachel; Edwards, Caitlin E; Tse, Longping V; Okuda, Kenichi; Markmann, Alena J; Bartelt, Luther; de Silva, Aravinda; Margolis, David M; Boucher, Richard C; Randell, Scott H; Suzuki, Tadaki; Gralinski, Lisa E; Kawaoka, Yoshihiro; Baric, Ralph S.
  • Hou YJ; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Chiba S; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
  • Halfmann P; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
  • Ehre C; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Kuroda M; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
  • Dinnon KH; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Schäfer A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Nakajima N; Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
  • Takahashi K; Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
  • Lee RE; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Mascenik TM; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Graham R; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Edwards CE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Tse LV; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Okuda K; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Markmann AJ; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Bartelt L; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • de Silva A; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Margolis DM; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Boucher RC; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Randell SH; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Suzuki T; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Gralinski LE; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Kawaoka Y; Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Science ; 370(6523): 1464-1468, 2020 12 18.
Article in English | MEDLINE | ID: covidwho-922513
ABSTRACT
The spike aspartic acid-614 to glycine (D614G) substitution is prevalent in global severe acute respiratory syndrome coronavirus 2 (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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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Variants Limits: Animals / Humans Language: English Journal: Science Year: 2020 Document Type: Article Affiliation country: Science.abe8499

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Variants Limits: Animals / Humans Language: English Journal: Science Year: 2020 Document Type: Article Affiliation country: Science.abe8499