IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro
Caterina Prelli Bozzo, Rayhane Nchioua, Meta Volčič, Lennart Koepke, Jana Krüger, Desirée Schütz, Sandra Heller, Christina M. Stürzel, Dorota Kmieć, Carina Conzelmann, Janis A. Müller, Fabian Zech, Elisabeth Braun, Rüdiger Groß, Lukas Wettstein, Tatjana Weil, Johanna Weiß, Federica Diofano, Armando Rodríguez, Sebastian Wiese, Daniel Sauter, Jan Münch, Christine Goffinet, Alberto Catanese, Michael P. Schön, Tobias M. Boeckers, Steffen Stenger, Kei Sato, Steffen Just, Alexander Kleger, Konstantin M. J. Sparrer, Frank Kirchhoff
Abstract
Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) can restrict viral pathogens, but pro- and anti-viral activities have been reported for coronaviruses. Here, we show that artificial overexpression of IFITMs blocks SARS-CoV-2 infection. However, endogenous IFITM expression supports efficient infection of SARS-CoV-2 in human lung cells. Our results indicate that the SARS-CoV-2 Spike protein interacts with IFITMs and hijacks them for efficient viral infection. IFITM proteins were expressed and further induced by interferons in human lung, gut, heart and brain cells. IFITM-derived peptides and targeting antibodies inhibit SARS-CoV-2 entry and replication in human lung cells, cardiomyocytes and gut organoids. Our results show that IFITM proteins are cofactors for efficient SARS-CoV-2 infection of human cell types representing in vivo targets for viral transmission, dissemination and pathogenesis and are potential targets for therapeutic approaches.