IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro.

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.

• Authors: Caterina Prelli Bozzo, Rayhane Nchioua, Meta Volcic, Lennart Koepke, Jana Krüger, Desiree Schütz, Sandra Heller, Christina M Stürzel, Dorota Kmiec, Carina Conzelmann, Janis Müller, Fabian Zech, Elisabeth Braun, Rüdiger Groß, Lukas Wettstein, Tatjana Weil, Johanna Weiß, Federica Diofano, Armando A Rodríguez Alfonso, Sebastian Wiese, Daniel Sauter, Jan Münch, Christine Goffinet, Alberto Catanese, Michael Schön, Tobias M Boeckers, Steffen Stenger, Kei Sato, Steffen Just, Alexander Kleger, Konstantin M J Sparrer, Frank Kirchhoff
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 4584 (07 28 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 34321474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• 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

Topics

• Amino Acid Sequence
• Angiotensin-Converting Enzyme 2 (antagonists & inhibitors, genetics, metabolism)
• Antibodies, Neutralizing (pharmacology)
• Antigens, Differentiation (genetics, metabolism)
• Binding Sites
• COVID-19 (virology)
• Gene Expression Regulation
• Host-Pathogen Interactions (drug effects, genetics)
• Humans
• Interferon-beta (pharmacology)
• Membrane Proteins (antagonists & inhibitors, genetics, metabolism)
• Protein Binding
• Protein Interaction Domains and Motifs
• RNA, Small Interfering (genetics, metabolism)
• RNA-Binding Proteins (antagonists & inhibitors, genetics, metabolism)
• SARS-CoV-2 (drug effects, genetics, metabolism)
• Sequence Alignment
• Sequence Homology, Amino Acid
• Spike Glycoprotein, Coronavirus (genetics, metabolism)
• Virus Attachment (drug effects)