The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types
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Open Access
- 11 February 2021
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
A novel variant of the SARS-CoV-2 virus carrying a point mutation in the Spike protein (D614G) has recently emerged and rapidly surpassed others in prevalence. This mutation is in linkage disequilibrium with an ORF1b protein variant (P314L), making it difficult to discern the functional significance of the Spike D614G mutation from population genetics alone. Here, we perform site-directed mutagenesis on wild-type human codon optimized Spike to introduce the D614G variant. Using multiple human cell lines, including human lung epithelial cells, we found that the lentiviral particles pseudotyped with Spike D614G are more effective at transducing cells than ones pseudotyped with wild-type Spike. The increased transduction with Spike D614G ranged from 1.3 to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2, and 1.5 to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Furthermore, trans-complementation of SARS-CoV-2 virus with Spike D614G showed an increased infectivity of human cells. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, we show that the G614 variant is more resistant to proteolytic cleavage in human cells, suggesting a possible mechanism for the increased transduction.Keywords
Funding Information
- American Heart Association (20POST35220040)
- National Institute of Allergy and Infectious Diseases (R01AI123155)
- Pew Charitable Trusts (PEW-00033055)
- Searle Scholars Program (SSP-2018-2737)
- National Institute of Allergy and Infectious Diseases (R01AI147131)
- Defense Advanced Research Projects Agency (HR0011-20-2-0040)
- National Human Genome Research Institute (DP2HG010099)
- National Cancer Institute (R01CA218668)
- Defense Advanced Research Projects Agency (D18AP00053)
- Sidney Kimmel Foundation
- Melanoma Research Alliance
- Brain and Behavior Research Foundation
- NIH (R00HG008171)
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