PT  - JOURNAL ARTICLE
AU  - Julian Buchrieser
AU  - Jeremy Dufloo
AU  - Mathieu Hubert
AU  - Blandine Monel
AU  - Delphine Planas
AU  - Maaran Michael Rajah
AU  - Cyril Planchais
AU  - Françoise Porrot
AU  - Florence Guivel-Benhassine
AU  - Sylvie Van der Werf
AU  - Nicoletta Casartelli
AU  - Hugo Mouquet
AU  - Timothée Bruel
AU  - Olivier Schwartz
TI  - Syncytia formation by SARS-CoV-2 infected cells
AID  - 10.1101/2020.07.14.202028
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.14.202028
4099  - http://biorxiv.org/content/early/2020/07/14/2020.07.14.202028.short
4100  - http://biorxiv.org/content/early/2020/07/14/2020.07.14.202028.full
AB  - 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 viral Spike protein (S) at their surface and fuse with ACE2-positive neighbouring cells. Expression of S without any other viral proteins triggers syncytia formation. Type-I interferon (IFN)-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 the pathological effects of SARS-CoV-2 are modulated by cellular proteins that either inhibit or facilitate syncytia formation.One Sentence Summary Syncytia produced by SARS-CoV-2 infected cells and regulation of their formation by IFITMs and TMPRSS2.Competing Interest StatementThe authors have declared no competing interest.