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The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types

View ORCID ProfileZharko Daniloski, View ORCID ProfileTristan X. Jordan, View ORCID ProfileJuliana K. Ilmain, View ORCID ProfileXinyi Guo, View ORCID ProfileGira Bhabha, View ORCID ProfileBenjamin R. tenOever, View ORCID ProfileNeville E. Sanjana
doi: https://doi.org/10.1101/2020.06.14.151357
Zharko Daniloski
1New York Genome Center, New York, NY, USA
2Department of Biology, New York University, New York, NY, USA
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Tristan X. Jordan
3Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Juliana K. Ilmain
4Department of Cell Biology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA
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Xinyi Guo
1New York Genome Center, New York, NY, USA
2Department of Biology, New York University, New York, NY, USA
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Gira Bhabha
4Department of Cell Biology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA
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Benjamin R. tenOever
3Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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  • For correspondence: benjamin.tenoever@mssm.edu neville@sanjanalab.org
Neville E. Sanjana
1New York Genome Center, New York, NY, USA
2Department of Biology, New York University, New York, NY, USA
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  • ORCID record for Neville E. Sanjana
  • For correspondence: benjamin.tenoever@mssm.edu neville@sanjanalab.org
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Abstract

A novel isolate 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 to introduce the D614G variant and show that in multiple cell lines, including human lung epithelial cells, that the D614G mutation is up to 8-fold more effective at transducing cells than wild-type. We demonstrate increased infection using both Spike-pseudotyped lentivirus and intact SARS-CoV-2 virus. Although there is minimal difference in ACE2 receptor binding between the Spike variants, we show that the G614 variant is more resistant to proteolytic cleavage in vitro and in human cells, suggesting a possible mechanism for the increased transduction. This result has important implications for the efficacy of Spike-based vaccines currently under development in protecting against this recent and highly-prevalent SARS-CoV-2 isolate.

Competing Interest Statement

The authors have declared no competing interest.

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Posted July 07, 2020.
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The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types
Zharko Daniloski, Tristan X. Jordan, Juliana K. Ilmain, Xinyi Guo, Gira Bhabha, Benjamin R. tenOever, Neville E. Sanjana
bioRxiv 2020.06.14.151357; doi: https://doi.org/10.1101/2020.06.14.151357
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The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types
Zharko Daniloski, Tristan X. Jordan, Juliana K. Ilmain, Xinyi Guo, Gira Bhabha, Benjamin R. tenOever, Neville E. Sanjana
bioRxiv 2020.06.14.151357; doi: https://doi.org/10.1101/2020.06.14.151357

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