Journal Article

DZNE-2021-01374

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro.

Prelli Bozzo, C. ; Nchioua, R. ; Volcic, M. ; Koepke, L. ; Krüger, J. ; Schütz, D. ; Heller, S. ; Stürzel, C. M. ; Kmiec, D. ; Conzelmann, C. ; Müller, J. ; Zech, F. ; Braun, E. ; Groß, R. ; Wettstein, L. ; Weil, T. ; Weiß, J. ; Diofano, F. ; Rodríguez Alfonso, A. A. ; Wiese, S. ; Sauter, D. ; Münch, J. ; Goffinet, C. ; Catanese, A. ; Schön, M. ; Böckers, T.DZNE* ; Stenger, S. ; Sato, K. ; Just, S. ; Kleger, A. ; Sparrer, K. M. J. ; Kirchhoff, F.

2021
Nature Publishing Group UK [London]

This record in other databases:    

Please use a persistent id in citations: 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.

Keyword(s): Amino Acid Sequence (MeSH) ; Angiotensin-Converting Enzyme 2: antagonists & inhibitors (MeSH) ; Angiotensin-Converting Enzyme 2: genetics (MeSH) ; Angiotensin-Converting Enzyme 2: metabolism (MeSH) ; Antibodies, Neutralizing: pharmacology (MeSH) ; Antigens, Differentiation: genetics (MeSH) ; Antigens, Differentiation: metabolism (MeSH) ; Binding Sites (MeSH) ; COVID-19: virology (MeSH) ; Gene Expression Regulation (MeSH) ; Host-Pathogen Interactions: drug effects (MeSH) ; Host-Pathogen Interactions: genetics (MeSH) ; Humans (MeSH) ; Interferon-beta: pharmacology (MeSH) ; Membrane Proteins: antagonists & inhibitors (MeSH) ; Membrane Proteins: genetics (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Protein Binding (MeSH) ; Protein Interaction Domains and Motifs (MeSH) ; RNA, Small Interfering: genetics (MeSH) ; RNA, Small Interfering: metabolism (MeSH) ; RNA-Binding Proteins: antagonists & inhibitors (MeSH) ; RNA-Binding Proteins: genetics (MeSH) ; RNA-Binding Proteins: metabolism (MeSH) ; SARS-CoV-2: drug effects (MeSH) ; SARS-CoV-2: genetics (MeSH) ; SARS-CoV-2: metabolism (MeSH) ; Sequence Alignment (MeSH) ; Sequence Homology, Amino Acid (MeSH) ; Spike Glycoprotein, Coronavirus: genetics (MeSH) ; Spike Glycoprotein, Coronavirus: metabolism (MeSH) ; Virus Attachment: drug effects (MeSH) ; Antibodies, Neutralizing ; Antigens, Differentiation ; IFITM2 protein, human ; IFITM3 protein, human ; Membrane Proteins ; RNA, Small Interfering ; RNA-Binding Proteins ; Spike Glycoprotein, Coronavirus ; leu-13 antigen ; spike protein, SARS-CoV-2 ; Interferon-beta ; ACE2 protein, human ; Angiotensin-Converting Enzyme 2

Note: CC BY

---

Contributing Institute(s):

1. Translational protein biochemistry (AG Böckers)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2021

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---