The impact of S2 mutations on Omicron SARS-CoV-2 cell surface expression and fusogenicity
| Title: | The impact of S2 mutations on Omicron SARS-CoV-2 cell surface expression and fusogenicity |
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| Authors: | Alba Escalera, Manon Laporte, Sam Turner, Umut Karakus, Ana S. Gonzalez-Reiche, Adriana van de Guchte, Keith Farrugia, Zain Khalil, Harm van Bakel, Derek Smith, Adolfo García-Sastre, Teresa Aydillo |
| Source: | Emerging Microbes and Infections, Vol 13, Iss 1 (2024) |
| Publisher Information: | Taylor & Francis Group, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Infectious and parasitic diseases LCC:Microbiology |
| Subject Terms: | SARS-CoV-2, Omicron, spike, cell–cell fusion, spike cell surface expression, “first-generation” Omicron sublineages, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502 |
| More Details: | SARS-CoV-2 Omicron subvariants are still emerging and spreading worldwide. These variants contain a high number of polymorphisms in the spike (S) glycoprotein that could potentially impact their pathogenicity and transmission. We have previously shown that the S:655Y and P681H mutations enhance S protein cleavage and syncytia formation. Interestingly, these polymorphisms are present in Omicron S protein. Here, we characterized the cleavage efficiency and fusogenicity of the S protein of different Omicron sublineages. Our results showed that Omicron BA.1 subvariant is efficiently cleaved but it is poorly fusogenic compared to previous SARS-CoV-2 strains. To understand the basis of this phenotype, we generated chimeric S protein using combinations of the S1 and S2 domains from WA1, Delta and Omicron BA.1 variants. We found that the S2 domain of Omicron BA.1 hindered efficient cell–cell fusion. Interestingly, this domain only contains six unique polymorphisms never detected before in ancestral SARS-CoV-2 variants. WA1614G S proteins containing the six individuals S2 Omicron mutations were assessed for their fusogenicity and S surface expression after transfection in cells. Results showed that the S:N856K and N969K substitutions decreased syncytia formation and impacted S protein cell surface levels. However, we observed that “first-generation” Omicron sublineages that emerged subsequently, had convergently evolved to an enhanced fusogenic activity and S expression on the surface of infected cells while “second-generation” Omicron variants have highly diverged and showed lineage-specific fusogenic properties. Importantly, our findings could have potential implications in the improvement and redesign of COVID-19 vaccines. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 22221751 2222-1751 |
| Relation: | https://doaj.org/toc/2222-1751 |
| DOI: | 10.1080/22221751.2023.2297553 |
| Access URL: | https://doaj.org/article/dd636ff1dfcb4a6788fca9dc5eec9110 |
| Accession Number: | edsdoj.636ff1dfcb4a6788fca9dc5eec9110 |
| Database: | Directory of Open Access Journals |
| ISSN: | 22221751 |
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| DOI: | 10.1080/22221751.2023.2297553 |
| Published in: | Emerging Microbes and Infections |
| Language: | English |