SARS‐CoV‐2 Alpha, Beta, and Delta variants display enhanced Spike‐mediated syncytia formation
Top Cited Papers
- 25 October 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 40 (24), e108944
- https://doi.org/10.15252/embj.2021108944
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 (B.1.1.7) and Beta (B.1.351) spread and fusion in cell cultures, compared to 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 to 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.Keywords
Funding Information
- Agence Nationale de Recherches sur le Sida et les Hépatites Virales
- Fondation pour la Recherche Médicale
- Institut National de la Santé et de la Recherche Médicale
- Fondation de France (00106077)
This publication has 85 references indexed in Scilit:
- More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteinsRetrovirology, 2017
- A new cell-based assay to evaluate myogenesis in mouse myoblast C2C12 cellsExperimental Cell Research, 2015
- IFITM Proteins Incorporated into HIV-1 Virions Impair Viral Fusion and SpreadCell Host & Microbe, 2014
- Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia FormationPLOS ONE, 2013
- Human Coronavirus HKU1 Infection of Primary Human Type II Alveolar Epithelial Cells: Cytopathic Effects and Innate Immune ResponsePLOS ONE, 2013
- Differential Cell Line Susceptibility to the Emerging Novel Human Betacoronavirus 2c EMC/2012: Implications for Disease Pathogenesis and Clinical ManifestationThe Journal of Infectious Diseases, 2013
- Differential maturation and subcellular localization of severe acute respiratory syndrome coronavirus surface proteins S, M and EJournal of General Virology, 2005
- Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirusNature, 2003
- Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from SingaporeHuman Pathology, 2003