tetano
Editor, Senior Moderator
Nat Commun
. 2021 Jul 28;12(1):4584.
doi: 10.1038/s41467-021-24817-y.
IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro
Caterina Prelli Bozzo[SUP] #[/SUP][SUP] 1 [/SUP], Rayhane Nchioua[SUP] #[/SUP][SUP] 1 [/SUP], Meta Volcic[SUP] 1 [/SUP], Lennart Koepke[SUP] 1 [/SUP], Jana Krüger[SUP] 2 [/SUP], Desiree Schütz[SUP] 1 [/SUP], Sandra Heller[SUP] 2 [/SUP], Christina M Stürzel[SUP] 1 [/SUP], Dorota Kmiec[SUP] 1 3 [/SUP], Carina Conzelmann[SUP] 1 [/SUP], Janis Müller[SUP] 1 [/SUP], Fabian Zech[SUP] 1 [/SUP], Elisabeth Braun[SUP] 1 [/SUP], Rüdiger Groß[SUP] 1 [/SUP], Lukas Wettstein[SUP] 1 [/SUP], Tatjana Weil[SUP] 1 [/SUP], Johanna Weiß[SUP] 1 [/SUP], Federica Diofano[SUP] 4 [/SUP], Armando A Rodríguez Alfonso[SUP] 5 6 [/SUP], Sebastian Wiese[SUP] 6 [/SUP], Daniel Sauter[SUP] 1 7 [/SUP], Jan Münch[SUP] 1 [/SUP], Christine Goffinet[SUP] 8 [/SUP], Alberto Catanese[SUP] 9 [/SUP], Michael Schön[SUP] 9 [/SUP], Tobias M Boeckers[SUP] 9 10 [/SUP], Steffen Stenger[SUP] 11 [/SUP], Kei Sato[SUP] 12 [/SUP], Steffen Just[SUP] 4 [/SUP], Alexander Kleger[SUP] 2 [/SUP], Konstantin M J Sparrer[SUP] 13 [/SUP], Frank Kirchhoff[SUP] 14 [/SUP]
Affiliations
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 Jul 28;12(1):4584.
doi: 10.1038/s41467-021-24817-y.
IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro
Caterina Prelli Bozzo[SUP] #[/SUP][SUP] 1 [/SUP], Rayhane Nchioua[SUP] #[/SUP][SUP] 1 [/SUP], Meta Volcic[SUP] 1 [/SUP], Lennart Koepke[SUP] 1 [/SUP], Jana Krüger[SUP] 2 [/SUP], Desiree Schütz[SUP] 1 [/SUP], Sandra Heller[SUP] 2 [/SUP], Christina M Stürzel[SUP] 1 [/SUP], Dorota Kmiec[SUP] 1 3 [/SUP], Carina Conzelmann[SUP] 1 [/SUP], Janis Müller[SUP] 1 [/SUP], Fabian Zech[SUP] 1 [/SUP], Elisabeth Braun[SUP] 1 [/SUP], Rüdiger Groß[SUP] 1 [/SUP], Lukas Wettstein[SUP] 1 [/SUP], Tatjana Weil[SUP] 1 [/SUP], Johanna Weiß[SUP] 1 [/SUP], Federica Diofano[SUP] 4 [/SUP], Armando A Rodríguez Alfonso[SUP] 5 6 [/SUP], Sebastian Wiese[SUP] 6 [/SUP], Daniel Sauter[SUP] 1 7 [/SUP], Jan Münch[SUP] 1 [/SUP], Christine Goffinet[SUP] 8 [/SUP], Alberto Catanese[SUP] 9 [/SUP], Michael Schön[SUP] 9 [/SUP], Tobias M Boeckers[SUP] 9 10 [/SUP], Steffen Stenger[SUP] 11 [/SUP], Kei Sato[SUP] 12 [/SUP], Steffen Just[SUP] 4 [/SUP], Alexander Kleger[SUP] 2 [/SUP], Konstantin M J Sparrer[SUP] 13 [/SUP], Frank Kirchhoff[SUP] 14 [/SUP]
Affiliations
- PMID: 34321474
- 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.