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.
© 2021. The Author(s).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Angiotensin-Converting Enzyme 2 / antagonists & inhibitors
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Angiotensin-Converting Enzyme 2 / genetics*
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Angiotensin-Converting Enzyme 2 / metabolism
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Antibodies, Neutralizing / pharmacology
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Antigens, Differentiation / genetics*
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Antigens, Differentiation / metabolism
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Binding Sites
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COVID-19 / virology
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Gene Expression Regulation
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Host-Pathogen Interactions / drug effects
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Host-Pathogen Interactions / genetics
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Humans
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Interferon-beta / pharmacology
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Protein Binding
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Protein Interaction Domains and Motifs
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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RNA-Binding Proteins / antagonists & inhibitors
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism
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SARS-CoV-2 / drug effects
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SARS-CoV-2 / genetics*
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SARS-CoV-2 / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
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Spike Glycoprotein, Coronavirus / genetics*
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Spike Glycoprotein, Coronavirus / metabolism
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Virus Attachment / drug effects
Substances
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Antibodies, Neutralizing
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Antigens, Differentiation
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IFITM2 protein, human
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IFITM3 protein, human
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Membrane Proteins
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RNA, Small Interfering
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RNA-Binding Proteins
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Spike Glycoprotein, Coronavirus
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leu-13 antigen
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spike protein, SARS-CoV-2
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Interferon-beta
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2