Nat Commun
. 2021 Jul 28;12(1):4584.
doi: 10.1038/s41467-021-24817-y.
IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro
Caterina Prelli Bozzo # 1 , Rayhane Nchioua # 1 , Meta Volcic 1 , Lennart Koepke 1 , Jana Krüger 2 , Desiree Schütz 1 , Sandra Heller 2 , Christina M Stürzel 1 , Dorota Kmiec 1 3 , Carina Conzelmann 1 , Janis Müller 1 , Fabian Zech 1 , Elisabeth Braun 1 , Rüdiger Groß 1 , Lukas Wettstein 1 , Tatjana Weil 1 , Johanna Weiß 1 , Federica Diofano 4 , Armando A Rodríguez Alfonso 5 6 , Sebastian Wiese 6 , Daniel Sauter 1 7 , Jan Münch 1 , Christine Goffinet 8 , Alberto Catanese 9 , Michael Schön 9 , Tobias M Boeckers 9 10 , Steffen Stenger 11 , Kei Sato 12 , Steffen Just 4 , Alexander Kleger 2 , Konstantin M J Sparrer 13 , Frank Kirchhoff 14
Affiliations
- PMID: 34321474
- DOI: 10.1038/s41467-021-24817-y
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.