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SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo
Author(s) -
Yixuan J. Hou,
S. Chiba,
Peter Halfmann,
Camille Ehré,
Makoto Kuroda,
Kenneth H. Din,
Sarah R. Leist,
Alexandra Schäfer,
Noriko Nakajima,
Kenta Takahashi,
Rhianna E. Lee,
Teresa Mascenik,
Rachel L. Graham,
Caitlin E. Edwards,
Longping V. Tse,
Kenichi Okuda,
Alena J. Markmann,
Luther A. Bartelt,
Aravinda de Silva,
David M. Margolis,
Richard C. Boucher,
Scott H. Randell,
Tadaki Suzuki,
Lisa E. Gralinski,
Yoshihiro Kawaoka,
Ralph S. Baric
Publication year - 2020
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.abe8499
Subject(s) - biology , virology , ex vivo , viral replication , virus , in vivo , infectivity , nidovirales , coronavirus , immunology , genetics , disease , covid-19 , medicine , infectious disease (medical specialty)
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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