4.7 Review

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

Journal

JOURNAL OF MOLECULAR BIOLOGY
Volume 434, Issue 6, Pages -

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2021.167280

Keywords

SARS-CoV-2; syncytia; cell-cell fusion; coronavirus; spike

Funding

  1. Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur
  2. ANRS
  3. Vaccine Research Institute [ANR-10-LABX-77]
  4. Fondation Pour la Recherche Medicale (FRM), Labex IBEID [ANR-10-LABX62-IBEID]
  5. ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR
  6. Pasteur-Paris University (PPU) International Doctoral Program
  7. Institut Pasteur Department of Virology Bourse de Soudure fellowship

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Syncytia play an important role in SARS-CoV-2 infection and pathology, potentially influencing the disease process through various mechanisms. Variants of concern have mutations in the S protein that enhance receptor interaction and fusogenicity. Several genes in the innate immune system act as barriers to syncytia formation. Understanding the fusogenicity of the Spike protein contributes to the understanding of SARS-CoV-2 infection and pathology.
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 molec-ular determinants of S mediated fusion and the antiviral innate immunity components that counteract syn-cytia 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. (c) 2021 Elsevier Ltd. All rights reserved.

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