RT Journal Article SR Electronic T1 SARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivo JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.09.28.317685 DO 10.1101/2020.09.28.317685 A1 Yixuan J. Hou A1 Shiho Chiba A1 Peter Halfmann A1 Camille Ehre A1 Makoto Kuroda A1 Kenneth H Dinnon III A1 Sarah R. Leist A1 Alexandra Schäfer A1 Noriko Nakajima A1 Kenta Takahashi A1 Rhianna E. Lee A1 Teresa M. Mascenik A1 Caitlin E. Edwards A1 Longping V. Tse A1 Richard C. Boucher A1 Scott H. Randell A1 Tadaki Suzuki A1 Lisa E. Gralinski A1 Yoshihiro Kawaoka A1 Ralph S. Baric YR 2020 UL http://biorxiv.org/content/early/2020/09/29/2020.09.28.317685.abstract AB The D614G substitution in the S protein is most prevalent SARS-CoV-2 strain circulating globally, but its effects in viral pathogenesis and transmission remain unclear. We engineered SARS-CoV-2 variants harboring the D614G substitution with or without nanoluciferase. The D614G variant replicates more efficiency in primary human proximal airway epithelial cells and is more fit than wildtype (WT) virus in competition studies. With similar morphology to the WT virion, the D614G virus is also more sensitive to SARS-CoV-2 neutralizing antibodies. Infection of human ACE2 transgenic mice and Syrian hamsters with the WT or D614G viruses produced similar titers in respiratory tissue and pulmonary disease. However, the D614G variant exhibited significantly faster droplet transmission between hamsters than the WT virus, early after infection. Our study demonstrated the SARS-CoV2 D614G substitution enhances infectivity, replication fitness, and early transmission.Competing Interest StatementThe authors have declared no competing interest.