| Title: |
IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro |
| Authors: |
Bozzo, Caterina Prelli; Nchioua, Rayhane; Volcic, Meta; Koepke, Lennart; Krüger, Jana; Schütz, Desiree; Heller, Sandra; Stürzel, Christina M.; Kmiec, Dorota; Conzelmann, Carina; Müller, Janis; Zech, Fabian; Braun, Elisabeth; Gross, Ruediger; Wettstein, Lukas; Weil, Tatjana; Weiss, Johanna; Diofano, Federica; Alfonso, Armando A. Rodriguez; Wiese, Sebastian; Sauter, Daniel; Münch, Jan; Goffinet, Christine; Catanese, Alberto; Schön, Michael; Böckers, Tobias M.; Stenger, Steffen; Sato, Kei; Just, Steffen; Kleger, Alexander; Sparrer, Konstantin M. J.; Kirchhoff, Frank |
| Publisher Information: |
Universität Ulm |
| Publication Year: |
2021 |
| Collection: |
OPARU (OPen Access Repository of Ulm University) |
| Subject Terms: |
Innate immunity; Viral infection; Fusion; Cells; Immunity; Innate; Virus diseases; SARS-CoV-2; Interferon inducers; Immunology; Angeborene Immunität; Virusinfektion; COVID-19; Interferon-Induktor |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| DOI: |
10.18725/OPARU-42012 |
| Availability: |
https://doi.org/10.18725/OPARU-42012; http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-42088-3 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.AD5C39BD |
| Database: |
BASE |