期刊
SCIENCE
卷 370, 期 6523, 页码 1464-1468出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abe8499
关键词
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资金
- U.S. National Institutes of Health [R01-AI110700, U54-CA260543, U01-AI151797, UM1-AI126619, R01-AI069274, HHSN272201700036I, HHSN272201400008C]
- Japan Agency for Medical Research and Development [JP19fk0108113, JP19fm0108006, JP20fk0108104, JP19fk0108110]
- North Carolina Policy Collaboratory at the University of North Carolina at Chapel Hill
- North Carolina Coronavirus Relief Fund by the North Carolina General Assembly
- NATIONAL CANCER INSTITUTE [U54CA260543] Funding Source: NIH RePORTER
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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