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.

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.