The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/65365 |
| _version_ | 1818028373766569984 |
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| author | Zharko Daniloski Tristan X Jordan Juliana K Ilmain Xinyi Guo Gira Bhabha Benjamin R tenOever Neville E Sanjana |
| author_facet | Zharko Daniloski Tristan X Jordan Juliana K Ilmain Xinyi Guo Gira Bhabha Benjamin R tenOever Neville E Sanjana |
| author_sort | Zharko Daniloski |
| collection | DOAJ |
| description | 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 from 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 in human cells. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction. |
| first_indexed | 2024-12-10T05:02:46Z |
| format | Article |
| id | doaj.art-320a762ee775429c8cf323a73659069a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:02:46Z |
| publishDate | 2021-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-320a762ee775429c8cf323a73659069a2022-12-22T02:01:21ZengeLife Sciences Publications LtdeLife2050-084X2021-02-011010.7554/eLife.65365The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell typesZharko Daniloski0https://orcid.org/0000-0002-3453-0849Tristan X Jordan1https://orcid.org/0000-0002-0602-2871Juliana K Ilmain2https://orcid.org/0000-0002-9507-5069Xinyi Guo3Gira Bhabha4https://orcid.org/0000-0003-0624-6178Benjamin R tenOever5https://orcid.org/0000-0003-0324-3078Neville E Sanjana6https://orcid.org/0000-0002-1504-0027New York Genome Center, New York, United States; Department of Biology, New York University, New York, United StatesDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Cell Biology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, United StatesNew York Genome Center, New York, United States; Department of Biology, New York University, New York, United StatesDepartment of Cell Biology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, United StatesDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, United StatesNew York Genome Center, New York, United States; Department of Biology, New York University, New York, United StatesA 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 from 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 in human cells. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction.https://elifesciences.org/articles/65365COVID-19SARS-CoV-2SpikeD614Gcoronavirus |
| spellingShingle | Zharko Daniloski Tristan X Jordan Juliana K Ilmain Xinyi Guo Gira Bhabha Benjamin R tenOever Neville E Sanjana The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types eLife COVID-19 SARS-CoV-2 Spike D614G coronavirus |
| title | The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types |
| title_full | The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types |
| title_fullStr | The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types |
| title_full_unstemmed | The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types |
| title_short | The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types |
| title_sort | spike d614g mutation increases sars cov 2 infection of multiple human cell types |
| topic | COVID-19 SARS-CoV-2 Spike D614G coronavirus |
| url | https://elifesciences.org/articles/65365 |
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