SARS-CoV-2 Alpha, Beta and Delta variants display enhanced Spike-mediated Syncytia Formation
Abstract Severe COVID-19 is characterized by lung abnormalities, including the presence of syncytial pneumocytes. Syncytia form when SARS-CoV-2 spike protein expressed on the surface of infected cells interacts with the ACE2 receptor on neighbouring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha and Beta spread and fusion in cell cultures. Alpha and Beta replicated similarly to D614G reference strain in Vero, Caco-2, Calu-3 and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Alpha, Beta and D614G fusion was similarly inhibited by interferon induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes differentially modified fusogenicity, binding to ACE2 and recognition by monoclonal antibodies. We further show that Delta spike also triggers faster fusion relative to D614G. Thus, SARS-CoV-2 emerging variants display enhanced syncytia formation.Synopsis The Spike protein of the novel SARS-CoV-2 variants are comparative more fusogenic than the earlier strains. The mutations in the variant spike protein differential modulate syncytia formation, ACE2 binding, and antibody escape.<jats:list list-type="bullet">The spike protein of Alpha, Beta and Delta, in the absence of other viral proteins, induce more syncytia than D614GThe ACE2 affinity of the variant spike proteins correlates to their fusogenicityVariant associated mutations P681H, D1118H, and D215G augment cell-cell fusion, while antibody escape mutation E484K, K417N and Δ242-244 hamper it.Variant spike-mediated syncytia formation is effectively restricted by IFITMs.
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 04. Nov. Zur Gesamtaufnahme - year:2023 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Rajah, Maaran Michael [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| doi: |
10.1101/2021.06.11.448011 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI031978738 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI031978738 | ||
| 003 | DE-627 | ||
| 005 | 20231205150338.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 210614s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2021.06.11.448011 |2 doi | |
| 035 | |a (DE-627)XBI031978738 | ||
| 035 | |a (biorXiv)10.1101/2021.06.11.448011 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Rajah, Maaran Michael |e verfasserin |0 (orcid)0000-0002-6674-8850 |4 aut | |
| 245 | 1 | 0 | |a SARS-CoV-2 Alpha, Beta and Delta variants display enhanced Spike-mediated Syncytia Formation |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Severe COVID-19 is characterized by lung abnormalities, including the presence of syncytial pneumocytes. Syncytia form when SARS-CoV-2 spike protein expressed on the surface of infected cells interacts with the ACE2 receptor on neighbouring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha and Beta spread and fusion in cell cultures. Alpha and Beta replicated similarly to D614G reference strain in Vero, Caco-2, Calu-3 and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Alpha, Beta and D614G fusion was similarly inhibited by interferon induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes differentially modified fusogenicity, binding to ACE2 and recognition by monoclonal antibodies. We further show that Delta spike also triggers faster fusion relative to D614G. Thus, SARS-CoV-2 emerging variants display enhanced syncytia formation.Synopsis The Spike protein of the novel SARS-CoV-2 variants are comparative more fusogenic than the earlier strains. The mutations in the variant spike protein differential modulate syncytia formation, ACE2 binding, and antibody escape.<jats:list list-type="bullet">The spike protein of Alpha, Beta and Delta, in the absence of other viral proteins, induce more syncytia than D614GThe ACE2 affinity of the variant spike proteins correlates to their fusogenicityVariant associated mutations P681H, D1118H, and D215G augment cell-cell fusion, while antibody escape mutation E484K, K417N and Δ242-244 hamper it.Variant spike-mediated syncytia formation is effectively restricted by IFITMs | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Hubert, Mathieu |4 aut | |
| 700 | 1 | |a Bishop, Elodie |4 aut | |
| 700 | 1 | |a Saunders, Nell |4 aut | |
| 700 | 1 | |a Robinot, Remy |4 aut | |
| 700 | 1 | |a Grzelak, Ludivine |4 aut | |
| 700 | 1 | |a Planas, Delphine |0 (orcid)0000-0002-2509-9954 |4 aut | |
| 700 | 1 | |a Dufloo, Jérémy |4 aut | |
| 700 | 1 | |a Gellenoncourt, Stacy |4 aut | |
| 700 | 1 | |a Bongers, Alice |4 aut | |
| 700 | 1 | |a Zivaljic, Marija |4 aut | |
| 700 | 1 | |a Planchais, Cyril |4 aut | |
| 700 | 1 | |a Guivel-Benhassine, Florence |4 aut | |
| 700 | 1 | |a Porrot, Françoise |4 aut | |
| 700 | 1 | |a Mouquet, Hugo |0 (orcid)0000-0002-4230-610X |4 aut | |
| 700 | 1 | |a Chakrabarti, Lisa |0 (orcid)0000-0002-1895-3630 |4 aut | |
| 700 | 1 | |a Buchrieser, Julian |0 (orcid)0000-0003-4790-7577 |4 aut | |
| 700 | 1 | |a Schwartz, Olivier |0 (orcid)0000-0002-0729-1475 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2023) vom: 04. Nov. |
| 773 | 1 | 8 | |g year:2023 |g day:04 |g month:11 |
| 856 | 4 | 0 | |u https://doi.org/10.15252/embj.2021108944 |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2021.06.11.448011 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 04 |c 11 | ||