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

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

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, 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 WieseDaniel 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

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141 Citations (Scopus)

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.

Original language	English
Article number	4584
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-24817-y
Publication status	Published - 1 Dec 2021
Externally published	Yes

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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., ... Kirchhoff, F. (2021). IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro. Nature Communications, 12(1), Article 4584. https://doi.org/10.1038/s41467-021-24817-y

@article{67f2aa64c09d427ca3493195ea7fc788,

title = "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.",

author = "\{Prelli Bozzo\}, Caterina and Rayhane Nchioua and Meta Volcic and Lennart Koepke and Jana Kr{\"u}ger and Desiree Sch{\"u}tz and Sandra Heller and St{\"u}rzel, \{Christina M.\} and Dorota Kmiec and Carina Conzelmann and Janis M{\"u}ller and Fabian Zech and Elisabeth Braun and R{\"u}diger Gro{\ss} and Lukas Wettstein and Tatjana Weil and Johanna Wei{\ss} and Federica Diofano and \{Rodr{\'i}guez Alfonso\}, \{Armando A.\} and Sebastian Wiese and Daniel Sauter and Jan M{\"u}nch and Christine Goffinet and Alberto Catanese and Michael Sch{\"o}n and Boeckers, \{Tobias M.\} and Steffen Stenger and Kei Sato and Steffen Just and Alexander Kleger and Sparrer, \{Konstantin M.J.\} and Frank Kirchhoff",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-021-24817-y",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

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Prelli Bozzo, C, Nchioua, R, Volcic, M, Koepke, L, Krüger, J, Schütz, D, Heller, S, Stürzel, CM, Kmiec, D, Conzelmann, C, Müller, J, Zech, F, Braun, E, Groß, R, Wettstein, L, Weil, T, Weiß, J, Diofano, F, Rodríguez Alfonso, AA, Wiese, S, Sauter, D, Münch, J, Goffinet, C, Catanese, A, Schön, M, Boeckers, TM, Stenger, S, Sato, K, Just, S, Kleger, A, Sparrer, KMJ & Kirchhoff, F 2021, 'IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro', Nature Communications, vol. 12, no. 1, 4584. https://doi.org/10.1038/s41467-021-24817-y

TY - JOUR

T1 - IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro

AU - Prelli Bozzo, Caterina

AU - Nchioua, Rayhane

AU - Volcic, Meta

AU - Koepke, Lennart

AU - Krüger, Jana

AU - Schütz, Desiree

AU - Heller, Sandra

AU - Stürzel, Christina M.

AU - Kmiec, Dorota

AU - Conzelmann, Carina

AU - Müller, Janis

AU - Zech, Fabian

AU - Braun, Elisabeth

AU - Groß, Rüdiger

AU - Wettstein, Lukas

AU - Weil, Tatjana

AU - Weiß, Johanna

AU - Diofano, Federica

AU - Rodríguez Alfonso, Armando A.

AU - Wiese, Sebastian

AU - Sauter, Daniel

AU - Münch, Jan

AU - Goffinet, Christine

AU - Catanese, Alberto

AU - Schön, Michael

AU - Boeckers, Tobias M.

AU - Stenger, Steffen

AU - Sato, Kei

AU - Just, Steffen

AU - Kleger, Alexander

AU - Sparrer, Konstantin M.J.

AU - Kirchhoff, Frank

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-021-24817-y

DO - 10.1038/s41467-021-24817-y

M3 - Article

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4584

ER -

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

Abstract

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