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Syncytia formation by SARS‐CoV‐2‐infected cells
pmc: PMC7646020 , PMC7849166
Syncytia formation by SARS‐CoV‐2‐infected cells
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.
- Université Paris Diderot France
- Institut Pasteur France
- Inserm France
- Vaccine Research Institute France
- New Sorbonne University France
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
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
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
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
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