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Syncytia formation by SARS‐CoV‐2‐infected cells
Author(s) -
Buchrieser Julian,
Dufloo Jérémy,
Hubert Mathieu,
Monel Blandine,
Planas Delphine,
Rajah Maaran Michael,
Planchais Cyril,
Porrot Françoise,
GuivelBenhassine Florence,
Van der Werf Sylvie,
Casartelli Nicoletta,
Mouquet Hugo,
Bruel Timothée,
Schwartz Olivier
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020106267
Subject(s) - syncytium , biology , infectivity , cell fusion , virology , microbiology and biotechnology , multinucleate , viral entry , transmembrane protein , virus , serine protease , cell , protease , viral replication , genetics , biochemistry , receptor , enzyme
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.