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Syncytia formation by SARS‐CoV‐2‐infected cells

Authors: Julian Buchrieser; Jérémy Dufloo; Mathieu Hubert; Blandine Monel; Delphine Planas; Maaran Michael Rajah; Cyril Planchais; +7 Authors

Syncytia formation by SARS‐CoV‐2‐infected cells

Abstract

Abstract Severe cases of COVID‐19 are associated with extensive lung damage and the presence of infected multinucleated syncytial pneumocytes. The viral and cellular mechanisms regulating the formation of these syncytia are not well understood. Here, we show that SARS‐CoV‐2‐infected cells express the Spike protein (S) at their surface and fuse with ACE2‐positive neighboring cells. Expression of S without any other viral proteins triggers syncytia formation. Interferon‐induced transmembrane proteins (IFITMs), a family of restriction factors that block the entry of many viruses, inhibit S‐mediated fusion, with IFITM1 being more active than IFITM2 and IFITM3. On the contrary, the TMPRSS2 serine protease, which is known to enhance infectivity of cell‐free virions, processes both S and ACE2 and increases syncytia formation by accelerating the fusion process. TMPRSS2 thwarts the antiviral effect of IFITMs. Our results show that SARS‐CoV‐2 pathological effects are modulated by cellular proteins that either inhibit or facilitate syncytia formation.

Cells infected with SARS‐CoV‐2 can fuse with neighbouring cells in a process accelerated by infectivity‐enhancing host factor TMPRSS2 and restricted by antiviral IFITM proteins.

Country
France
Subjects by Vocabulary

Microsoft Academic Graph classification: Interferon Syncytium Cell fusion Transmembrane protein Cell biology medicine.drug Biology medicine HEK 293 cells Membrane protein Cell culture Vero cell

Keywords

fusion, MESH: Spike Glycoprotein, Coronavirus, MESH: Angiotensin-Converting Enzyme 2, Giant Cells, SARS‐CoV‐2, Cell Fusion, MESH: Giant Cells, MESH: Chlorocebus aethiops, Chlorocebus aethiops, MESH: COVID-19, MESH: Animals, MESH: Serine Endopeptidases, General Neuroscience, Serine Endopeptidases, RNA-Binding Proteins, Articles, interferon, MESH: HEK293 Cells, MESH: Antigens, Differentiation, Host-Pathogen Interactions, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Angiotensin-Converting Enzyme 2, MESH: Membrane Proteins, Corrigendum, Immunology, MESH: Vero Cells, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, Animals, Humans, MESH: SARS-CoV-2, syncytia, Vero Cells, Molecular Biology, MESH: Humans, General Immunology and Microbiology, SARS-CoV-2, MESH: Host-Pathogen Interactions, COVID-19, Membrane Proteins, Antigens, Differentiation, MESH: Cell Line, HEK293 Cells, MESH: RNA-Binding Proteins, MESH: Cell Fusion

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    389
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 0.1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 1%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 0.01%
  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    389
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 0.1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 1%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 0.01%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
389
Top 0.1%
Top 1%
Top 0.01%
Green
bronze