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

Yixuan J. Hou(University of North Carolina at Chapel Hill), S. Chiba(University of Wisconsin–Madison), Peter Halfmann(University of Wisconsin–Madison), Camille Ehré(University of North Carolina at Chapel Hill), Makoto Kuroda(University of Wisconsin–Madison), Kenneth H. Dinnon(University of North Carolina at Chapel Hill), Sarah R. Leist(University of North Carolina at Chapel Hill), Alexandra Schäfer(University of North Carolina at Chapel Hill), Noriko Nakajima(National Institute of Infectious Diseases), Kenta Takahashi(National Institute of Infectious Diseases), Rhianna E. Lee(University of North Carolina at Chapel Hill), Teresa Mascenik(University of North Carolina at Chapel Hill), Rachel L. Graham(University of North Carolina at Chapel Hill), Caitlin E. Edwards(University of North Carolina at Chapel Hill), Longping V. Tse(University of North Carolina at Chapel Hill), Kenichi Okuda(University of North Carolina at Chapel Hill), Alena J. Markmann(University of North Carolina at Chapel Hill), Luther A. Bartelt(University of North Carolina at Chapel Hill), Aravinda de Silva(University of North Carolina at Chapel Hill), David M. Margolis(University of North Carolina at Chapel Hill), Richard C. Boucher(University of North Carolina at Chapel Hill), Scott H. Randell(University of North Carolina at Chapel Hill), Tadaki Suzuki(National Institute of Infectious Diseases), Lisa E. Gralinski(University of North Carolina at Chapel Hill), Yoshihiro Kawaoka(University of Wisconsin–Madison), Ralph S. Baric(University of North Carolina at Chapel Hill)
Science
November 12, 2020
10.1126/science.abe8499
Cited by 999Open Access
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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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