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

View ORCID ProfileZharko Daniloski, View ORCID ProfileXinyi Guo, 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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Xinyi Guo
1New York Genome Center, New York, NY, USA
2Department of Biology, New York University, New York, NY, USA
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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: neville@sanjanalab.org
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Abstract

Recently, a novel isolate of the SARS-CoV-2 virus carrying a point mutation in the Spike protein (D614G) has emerged and rapidly surpassed others in prevalence, including the original SARS-CoV-2 isolate from Wuhan, China. This Spike variant is a defining feature of the most prevalent clade (A2a) of SARS-CoV-2 genomes worldwide. Using phylogenomic data, several groups have proposed that the D614G variant may confer increased transmissibility leading to positive selection, while others have claimed that currently available evidence does not support positive selection. Furthermore, in the A2a clade, this mutation is in linkage disequilibrium with a 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 a human codon-optimized spike protein to introduce the D614G variant and produce SARS-CoV-2-pseudotyped lentiviral particles (S-Virus) with this variant and with D614 Spike. We show that in multiple cell lines, including human lung epithelial cells, that S-Virus carrying the D614G mutation is up to 8-fold more effective at transducing cells than wild-type S-Virus. This provides functional evidence that the D614G mutation in the Spike protein increases transduction of human cells. Further we show that the G614 variant is more resistant to cleavage in vitro and in human cells, which may suggest a possible mechanism for the increased transduction. Given that several vaccines in development and in clinical trials are based on the initial (D614) Spike sequence, this result has important implications for the efficacy of these vaccines in protecting against this recent and highly-prevalent SARS-CoV-2 isolate.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 15, 2020.
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The D614G mutation in SARS-CoV-2 Spike increases transduction of multiple human cell types
Zharko Daniloski, Xinyi Guo, Neville E. Sanjana
bioRxiv 2020.06.14.151357; doi: https://doi.org/10.1101/2020.06.14.151357
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The D614G mutation in SARS-CoV-2 Spike increases transduction of multiple human cell types
Zharko Daniloski, Xinyi Guo, Neville E. Sanjana
bioRxiv 2020.06.14.151357; doi: https://doi.org/10.1101/2020.06.14.151357

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