| Title: |
IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro. |
| Authors: |
Prelli Bozzo, Caterina; Nchioua, Rayhane; Müller, Janis; Zech, Fabian; Braun, Elisabeth; Groß, Rüdiger; Wettstein, Lukas; Weil, Tatjana; Weiß, Johanna; Diofano, Federica; Rodríguez Alfonso, Armando A; Wiese, Sebastian; Volcic, Meta; Sauter, Daniel; Münch, Jan; Goffinet, Christine; Catanese, Alberto; Schön, Michael; Böckers, Tobias; Stenger, Steffen; Sato, Kei; Just, Steffen; Kleger, Alexander; Koepke, Lennart; Sparrer, Konstantin M J; Kirchhoff, Frank; Krüger, Jana; Schütz, Desiree; Heller, Sandra; Stürzel, Christina M; Kmiec, Dorota; Conzelmann, Carina |
| Source: |
Nature Communications 12(1), 4584 (2021). doi:10.1038/s41467-021-24817-y |
| Publisher Information: |
Nature Publishing Group UK |
| Publication Year: |
2021 |
| Subject Terms: |
info:eu-repo/classification/ddc/500; Amino Acid Sequence; Angiotensin-Converting Enzyme 2: antagonists & inhibitors; Angiotensin-Converting Enzyme 2: genetics; Angiotensin-Converting Enzyme 2: metabolism; Antibodies; Neutralizing: pharmacology; Antigens; Differentiation: genetics; Differentiation: metabolism; Binding Sites; COVID-19: virology; Gene Expression Regulation; Host-Pathogen Interactions: drug effects; Host-Pathogen Interactions: genetics; Humans; Interferon-beta: pharmacology; Membrane Proteins: antagonists & inhibitors; Membrane Proteins: genetics; Membrane Proteins: metabolism; Protein Binding; Protein Interaction Domains and Motifs; RNA; Small Interfering: genetics; Small Interfering: metabolism; RNA-Binding Proteins: antagonists & inhibitors; RNA-Binding Proteins: genetics; RNA-Binding Proteins: metabolism; SARS-CoV-2: drug effects; SARS-CoV-2: genetics |
| Subject Geographic: |
DE |
| 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 |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
info:eu-repo/semantics/altIdentifier/issn/2041-1723; info:eu-repo/semantics/altIdentifier/pmid/pmid:34321474; https://pub.dzne.de/record/162717 |
| Availability: |
https://pub.dzne.de/record/162717; https://pub.dzne.de/search?p=id:%22DZNE-2021-01374%22 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.ADB9863E |
| Database: |
BASE |