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The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation

Syncytia are formed when individual cells fuse. SARS-CoV-2 induces syncytia when the viral spike (S) protein on the surface of an infected cell interacts with receptors on neighboring cells. Syncytia may potentially contribute to pathology by facilitating viral dissemination, cytopathicity, immune e...

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Autores principales: Rajah, Maaran Michael, Bernier, Annie, Buchrieser, Julian, Schwartz, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485708/
https://www.ncbi.nlm.nih.gov/pubmed/34606831
http://dx.doi.org/10.1016/j.jmb.2021.167280
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author Rajah, Maaran Michael
Bernier, Annie
Buchrieser, Julian
Schwartz, Olivier
author_facet Rajah, Maaran Michael
Bernier, Annie
Buchrieser, Julian
Schwartz, Olivier
author_sort Rajah, Maaran Michael
collection PubMed
description Syncytia are formed when individual cells fuse. SARS-CoV-2 induces syncytia when the viral spike (S) protein on the surface of an infected cell interacts with receptors on neighboring cells. Syncytia may potentially contribute to pathology by facilitating viral dissemination, cytopathicity, immune evasion, and inflammatory response. SARS-CoV-2 variants of concern possess several mutations within the S protein that enhance receptor interaction, fusogenicity and antibody binding. In this review, we discuss the molecular determinants of S mediated fusion and the antiviral innate immunity components that counteract syncytia formation. Several interferon-stimulated genes, including IFITMs and LY6E act as barriers to S protein-mediated fusion by altering the composition or biophysical properties of the target membrane. We also summarize the effect that the mutations associated with the variants of concern have on S protein fusogenicity. Altogether, this review contextualizes the current understanding of Spike fusogenicity and the role of syncytia during SARS-CoV-2 infection and pathology.
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spelling pubmed-84857082021-10-04 The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation Rajah, Maaran Michael Bernier, Annie Buchrieser, Julian Schwartz, Olivier J Mol Biol Review Article Syncytia are formed when individual cells fuse. SARS-CoV-2 induces syncytia when the viral spike (S) protein on the surface of an infected cell interacts with receptors on neighboring cells. Syncytia may potentially contribute to pathology by facilitating viral dissemination, cytopathicity, immune evasion, and inflammatory response. SARS-CoV-2 variants of concern possess several mutations within the S protein that enhance receptor interaction, fusogenicity and antibody binding. In this review, we discuss the molecular determinants of S mediated fusion and the antiviral innate immunity components that counteract syncytia formation. Several interferon-stimulated genes, including IFITMs and LY6E act as barriers to S protein-mediated fusion by altering the composition or biophysical properties of the target membrane. We also summarize the effect that the mutations associated with the variants of concern have on S protein fusogenicity. Altogether, this review contextualizes the current understanding of Spike fusogenicity and the role of syncytia during SARS-CoV-2 infection and pathology. Elsevier Ltd. 2022-03-30 2021-10-01 /pmc/articles/PMC8485708/ /pubmed/34606831 http://dx.doi.org/10.1016/j.jmb.2021.167280 Text en © 2021 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Review Article
Rajah, Maaran Michael
Bernier, Annie
Buchrieser, Julian
Schwartz, Olivier
The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation
title The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation
title_full The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation
title_fullStr The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation
title_full_unstemmed The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation
title_short The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation
title_sort mechanism and consequences of sars-cov-2 spike-mediated fusion and syncytia formation
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485708/
https://www.ncbi.nlm.nih.gov/pubmed/34606831
http://dx.doi.org/10.1016/j.jmb.2021.167280
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