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IFITM proteins promote SARS-CoV-2 infection of human lung cells

Caterina Prelli Bozzo, Rayhane Nchioua, Meta Volcic, Lukas Wettstein, Tatjana Weil, Jana Krüger, Sandra Heller, Carina Conzelmann, Janis Müller, Rüdiger Gross, Fabian Zech, Desiree Schütz, Lennart Koepke, Christina M Stuerzel, Christiane Schüler, Saskia Stenzel, Elisabeth Braun, Johanna Weiß, View ORCID ProfileDaniel Sauter, Jan Münch, Steffen Stenger, View ORCID ProfileKei Sato, Alexander Kleger, View ORCID ProfileChristine Goffinet, View ORCID ProfileKonstantin M.J. Sparrer, Frank Kirchhoff
doi: https://doi.org/10.1101/2020.08.18.255935
Caterina Prelli Bozzo
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Rayhane Nchioua
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Meta Volcic
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Lukas Wettstein
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Tatjana Weil
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Jana Krüger
2Department of Internal Medicine I, Ulm University Medical Centre, 89081 Ulm, Germany
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Sandra Heller
2Department of Internal Medicine I, Ulm University Medical Centre, 89081 Ulm, Germany
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Carina Conzelmann
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Janis Müller
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Rüdiger Gross
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Fabian Zech
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Desiree Schütz
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Lennart Koepke
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Christina M Stuerzel
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Christiane Schüler
3Institute of Virology, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany
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Saskia Stenzel
3Institute of Virology, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany
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Elisabeth Braun
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Johanna Weiß
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Daniel Sauter
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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  • ORCID record for Daniel Sauter
Jan Münch
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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Steffen Stenger
4Institute of Medical Microbiology and Hygiene Ulm University Medical Centre 89081 Ulm, Germany
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Kei Sato
5Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
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  • ORCID record for Kei Sato
Alexander Kleger
2Department of Internal Medicine I, Ulm University Medical Centre, 89081 Ulm, Germany
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Christine Goffinet
3Institute of Virology, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany
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  • ORCID record for Christine Goffinet
Konstantin M.J. Sparrer
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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  • ORCID record for Konstantin M.J. Sparrer
  • For correspondence: konstantin.sparrer@uni-ulm.de Frank.Kirchhoff@uni-ulm.de
Frank Kirchhoff
1Institute for Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany
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  • For correspondence: konstantin.sparrer@uni-ulm.de Frank.Kirchhoff@uni-ulm.de
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ABSTRACT

Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) restrict numerous viral pathogens and are thought to prevent infection by severe acute respiratory syndrome coronaviruses (SARS-CoVs). However, most evidence comes from single-round pseudoparticle infection of cells artificially overexpressing IFITMs. Here, we confirmed that overexpression of IFITMs blocks pseudoparticle infections mediated by the Spike proteins of β-coronaviruses including pandemic SARS-CoV-2. In striking contrast, however, endogenous IFITM expression promoted genuine SARS-CoV-2 infection in human lung cells both in the presence and absence of interferon. IFITM2 was most critical for efficient entry of SARS-CoV-2 and enhanced virus production from Calu-3 cells by several orders of magnitude. IFITMs are expressed and further induced by interferons in the lung representing the primary site of SARS-CoV-2 infection as well as in other relevant tissues. Our finding that IFITMs enhance SARS-CoV-2 infection under conditions approximating the in vivo situation shows that they may promote viral invasion during COVID-19.

HIGHLIGHTS

  • Overexpression of IFITM1, 2 and 3 restricts SARS-CoV-2 infection

  • Endogenous IFITM1, 2 and 3 boost SARS-CoV-2 infection of human lung cells

  • IFITM2 is critical for efficient entry of SARS-CoV-2 in Calu-3 cells

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 18, 2020.
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IFITM proteins promote SARS-CoV-2 infection of human lung cells
Caterina Prelli Bozzo, Rayhane Nchioua, Meta Volcic, Lukas Wettstein, Tatjana Weil, Jana Krüger, Sandra Heller, Carina Conzelmann, Janis Müller, Rüdiger Gross, Fabian Zech, Desiree Schütz, Lennart Koepke, Christina M Stuerzel, Christiane Schüler, Saskia Stenzel, Elisabeth Braun, Johanna Weiß, Daniel Sauter, Jan Münch, Steffen Stenger, Kei Sato, Alexander Kleger, Christine Goffinet, Konstantin M.J. Sparrer, Frank Kirchhoff
bioRxiv 2020.08.18.255935; doi: https://doi.org/10.1101/2020.08.18.255935
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IFITM proteins promote SARS-CoV-2 infection of human lung cells
Caterina Prelli Bozzo, Rayhane Nchioua, Meta Volcic, Lukas Wettstein, Tatjana Weil, Jana Krüger, Sandra Heller, Carina Conzelmann, Janis Müller, Rüdiger Gross, Fabian Zech, Desiree Schütz, Lennart Koepke, Christina M Stuerzel, Christiane Schüler, Saskia Stenzel, Elisabeth Braun, Johanna Weiß, Daniel Sauter, Jan Münch, Steffen Stenger, Kei Sato, Alexander Kleger, Christine Goffinet, Konstantin M.J. Sparrer, Frank Kirchhoff
bioRxiv 2020.08.18.255935; doi: https://doi.org/10.1101/2020.08.18.255935

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