Journal
CELL DISCOVERY
Volume 6, Issue 1, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41421-020-00226-1
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Funding
- Zhejiang Provincial Science and Technology Department [2020C03123-1]
- National Science and Technology Major Project for the Control and Prevention of Major Infectious Diseases in China [2018ZX10711001, 2018ZX10102001, 2018ZX10302206]
- Life Sciences Institute at Zhejiang University
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally with more than 33 million patients diagnosed, taking more than a million lives. Abundant mutations were observed but the functional consequences of these mutations are largely unknown. We report the mutation spectrum, replication dynamics, and infectivity of 11 patient-derived viral isolates in diverse cell lines, including the human lung cancer cell line Calu-3. We observed 46 mutations, including 9 different mutations in the spike gene. Importantly, these viral isolates show significant and consistent variations in replication dynamics and infectivity in tested cell lines, up to a 1500-fold difference in viral titers at 24h after infecting Calu-3 cells. Moreover, we show that the variations in viral titers among viral isolates are positively correlated with blood clotting function but inversely correlated with the amount of red blood cell and hemoglobin in patients. Therefore, we provide direct evidence that naturally occurring mutations in SARS-CoV-2 can substantially change its replication dynamics and infectivity in diverse human cell lines, with clinical implications in vivo.
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