%0 Journal Article %T Syncytia formation by SARS‐CoV‐2‐infected cells %+ Virus et Immunité - Virus and immunity (CNRS-UMR3569) %+ École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC) %+ Vaccine Research Institute [Créteil, France] (VRI) %+ Immunologie humorale - Humoral Immunology %+ Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)) %+ Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur) %A Buchrieser, Julian %A Dufloo, Jérémy %A Hubert, Mathieu %A Monel, Blandine %A Planas, Delphine %A Rajah, Maaran Michael %A Planchais, Cyril %A Porrot, Françoise %A Guivel-Benhassine, Florence %A van Der Werf, Sylvie %A Casartelli, Nicoletta %A Mouquet, Hugo %A Bruel, Timothée %A Schwartz, Olivier %Z OS laboratory is funded by Institut Pasteur, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), “TIMTAMDEN” ANR-14-CE14-0029, “CHIKV-Viro-Immuno” ANR-14-CE14-0015-01 and the Gilead HIV cure program, ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. Work in UPBI is funded by grant ANR-10-INSB-04-01 and Région Ile-de-France program DIM1-Health. HM laboratory is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), the INSERM, REACTing, and EU (RECOVER) grants. SVDW laboratory is funded by Institut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, and EU (RECOVER) grant. M.M.R is supported by the Pasteur-Paris University (PPU) International Doctoral Program. %Z We thank members of the Virus and Immunity Unit for discussions and help, Mauro Giacca for discussion and sharing unpublished results, Nathalie Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis, and Nicolas Escriou for the kind gift of anti-SARS-CoV-2 antibodies. %< avec comité de lecture %@ 0261-4189 %J EMBO Journal %I EMBO Press %V 39 %N 23 %P e106267 %8 2020-12 %D 2020 %R 10.15252/embj.2020106267 %M 33051876 %K SARS-CoV-2 %K fusion %K interferon %K syncytia %Z Life Sciences [q-bio]/Microbiology and Parasitology/VirologyJournal articles %X 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. %G English %L pasteur-03253133 %U https://pasteur.hal.science/pasteur-03253133 %~ INSERM %~ PASTEUR %~ CNRS %~ UPEC %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SCIENCES %~ ANR %~ FRM %~ HUMORAL-IMMUNOLOGY %~ U1222 %~ VIR-IMMUN %~ PASTEUR_UMR3569 %~ GMV-ARN