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Journal articles
SARS‐CoV‐2 Alpha, Beta, and Delta variants display enhanced Spike‐mediated syncytia formation
Maaran Michael Rajah
1, 2
Mathieu Hubert
1, 3
Elodie Bishop
1, 4
Nell Saunders
1
Remy Robinot
1
Ludivine Grzelak
1, 2
Delphine Planas
1, 3
Jérémy Dufloo
1, 2
Stacy Gellenoncourt
1, 2
Alice Bongers
1, 2
Marija Zivaljic
5, 6
Cyril Planchais
7
Florence Guivel-Benhassine
1
Françoise Porrot
1
Hugo Mouquet
7
Lisa Chakrabarti
1
Julian Buchrieser
1, *
Olivier Schwartz
1, 2, *
*
Corresponding author
Maaran Michael Rajah 1, 2
Author ORCID : https://orcid.org/0000-0002-6674-8850
Mathieu Hubert 1, 3
Author
Elodie Bishop 1, 4
Author
Nell Saunders 1
Author ORCID : https://orcid.org/0000-0002-0872-1529
Remy Robinot 1
Author
Ludivine Grzelak 1, 2
Author
Delphine Planas 1, 3
Author
Jérémy Dufloo 1, 2
Author ORCID : https://orcid.org/0000-0002-4963-1378
Stacy Gellenoncourt 1, 2
Author ORCID : https://orcid.org/0000-0003-1896-7212
Alice Bongers 1, 2
Author
Marija Zivaljic 5, 6
Author
Cyril Planchais 7
Author
Florence Guivel-Benhassine 1
Author
Françoise Porrot 1
Author
Hugo Mouquet 7
Author ORCID : https://orcid.org/0000-0002-4230-610X
Lisa A. Chakrabarti 1
Author IdHAL : lisa-chakrabarti ORCID : https://orcid.org/0000-0002-1895-3630
Julian Buchrieser 1
Correspondent author ORCID : https://orcid.org/0000-0003-4790-7577
Olivier Schwartz 1, 2
Correspondent author ORCID : https://orcid.org/0000-0002-0729-1475
1
Virus et Immunité - Virus and immunity (Département Virologie, 25-28 rue du Docteur Roux - 75724 Paris CEDEX15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR 3569 (France)
2
UPC - Université Paris Cité (85 boulevard Saint-Germain
75006 Paris - France)
3
VRI - Vaccine Research Institute (61 avenue du Général de Gaulle 94010 Créteil Cedex France - France)
- UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12 (61 avenue du Général de Gaulle - 94010 Créteil cedex - France)
4
SU - Sorbonne Université (21 rue de l’École de médecine - 75006 Paris - France)
5
NISC - Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (Département de Neuroscience - 25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR3571 (France)
- SU - Sorbonne Université (21 rue de l’École de médecine - 75006 Paris - France)
6
ED 158 - 3C - Ecole doctorale Cerveau Cognition et Comportement [Paris] (Sorbonne Université - Campus des Cordeliers
15, rue de l'école de médecine
75006 Paris - France)
- SU - Sorbonne Université (21 rue de l’École de médecine - 75006 Paris - France)
7
Immunologie humorale - Humoral Immunology (Département d'Immunologie
25-28, rue du Docteur Roux
75724 Paris cedex 15 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1222 (101, rue de Tolbiac, 75013 Paris - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
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 neighboring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha (B.1.1.7) and Beta (B.1.351) spread and fusion in cell cultures, compared with the ancestral D614G strain. Alpha and Beta replicated similarly to D614G strain in Vero, Caco-2, Calu-3, and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Variant spike proteins displayed higher ACE2 affinity compared with D614G. Alpha, Beta, and D614G fusion was similarly inhibited by interferon-induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes modified fusogenicity, binding to ACE2 or 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.
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Journal articles
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03654276
Contributor : Isma Ziani Connect in order to contact the contributor
Submitted on : Thursday, April 28, 2022 - 2:50:36 PM
Last modification on : Thursday, May 5, 2022 - 4:05:48 PM
Contributor : Isma Ziani Connect in order to contact the contributor
Submitted on : Thursday, April 28, 2022 - 2:50:36 PM
Last modification on : Thursday, May 5, 2022 - 4:05:48 PM
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- HAL Id : pasteur-03654276, version 1
- DOI : 10.15252/embj.2021108944
- PUBMED : 34601723
- PUBMEDCENTRAL : PMC8646911
Collections
PASTEUR | UPEC-UPEM | UPEC | ANR | CNRS | UNIV-PARIS | SORBONNE-UNIVERSITE | SU-MEDECINE | SU-TI | INSERM
Citation
Maaran Michael Rajah, Mathieu Hubert, Elodie Bishop, Nell Saunders, Remy Robinot, et al.. SARS‐CoV‐2 Alpha, Beta, and Delta variants display enhanced Spike‐mediated syncytia formation. EMBO Journal, EMBO Press, 2021, 40 (24), pp.e108944. ⟨10.15252/embj.2021108944⟩. ⟨pasteur-03654276⟩
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