IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-24817-y.html
   My bibliography  Save this article

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

Author

Listed:
  • Caterina Prelli Bozzo

    (Ulm University Medical Center)

  • Rayhane Nchioua

    (Ulm University Medical Center)

  • Meta Volcic

    (Ulm University Medical Center)

  • Lennart Koepke

    (Ulm University Medical Center)

  • Jana Krüger

    (Ulm University Medical Center)

  • Desiree Schütz

    (Ulm University Medical Center)

  • Sandra Heller

    (Ulm University Medical Center)

  • Christina M. Stürzel

    (Ulm University Medical Center)

  • Dorota Kmiec

    (Ulm University Medical Center
    King’s College London)

  • Carina Conzelmann

    (Ulm University Medical Center)

  • Janis Müller

    (Ulm University Medical Center)

  • Fabian Zech

    (Ulm University Medical Center)

  • Elisabeth Braun

    (Ulm University Medical Center)

  • Rüdiger Groß

    (Ulm University Medical Center)

  • Lukas Wettstein

    (Ulm University Medical Center)

  • Tatjana Weil

    (Ulm University Medical Center)

  • Johanna Weiß

    (Ulm University Medical Center)

  • Federica Diofano

    (Ulm University)

  • Armando A. Rodríguez Alfonso

    (Ulm University Medical Center
    Ulm University Medical Center)

  • Sebastian Wiese

    (Ulm University Medical Center)

  • Daniel Sauter

    (Ulm University Medical Center
    University Hospital Tübingen)

  • Jan Münch

    (Ulm University Medical Center)

  • Christine Goffinet

    (Charité—Universitätsmedizin Berlin)

  • Alberto Catanese

    (Ulm University)

  • Michael Schön

    (Ulm University)

  • Tobias M. Boeckers

    (Ulm University
    Ulm University)

  • Steffen Stenger

    (Ulm University Medical Center)

  • Kei Sato

    (The University of Tokyo)

  • Steffen Just

    (Ulm University)

  • Alexander Kleger

    (Ulm University Medical Center)

  • Konstantin M. J. Sparrer

    (Ulm University Medical Center)

  • Frank Kirchhoff

    (Ulm University Medical Center)

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.

Suggested Citation

  • 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 , 2021. "IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24817-y
    DOI: 10.1038/s41467-021-24817-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-24817-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-24817-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Tabea M. Eser & Olga Baranov & Manuel Huth & Mohammed I. M. Ahmed & Flora Deák & Kathrin Held & Luming Lin & Kami Pekayvaz & Alexander Leunig & Leo Nicolai & Georgios Pollakis & Marcus Buggert & David, 2023. "Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Guoli Shi & Tiansheng Li & Kin Kui Lai & Reed F. Johnson & Jonathan W. Yewdell & Alex A. Compton, 2024. "Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Catherine F. Hatton & Rachel A. Botting & Maria Emilia Dueñas & Iram J. Haq & Bernard Verdon & Benjamin J. Thompson & Jarmila Stremenova Spegarova & Florian Gothe & Emily Stephenson & Aaron I. Gardner, 2021. "Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    4. M. Clement & J. L. Forbester & M. Marsden & P. Sabberwal & M. S. Sommerville & D. Wellington & S. Dimonte & S. Clare & K. Harcourt & Z. Yin & L. Nobre & R. Antrobus & B. Jin & M. Chen & S. Makvandi-Ne, 2022. "IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24817-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.