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STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters

Author

Listed:
  • Robbert Boudewijns

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

  • Hendrik Jan Thibaut

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network
    Translational Platform Virology and Chemotherapy)

  • Suzanne J. F. Kaptein

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network)

  • Rong Li

    (Utah State University)

  • Valentijn Vergote

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Zoonotic Infectious Diseases Unit)

  • Laura Seldeslachts

    (KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC)

  • Johan Weyenbergh

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation)

  • Carolien Keyzer

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

  • Lindsey Bervoets

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network)

  • Sapna Sharma

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

  • Laurens Liesenborghs

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

  • Ji Ma

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

  • Sander Jansen

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

  • Dominique Looveren

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network
    Translational Platform Virology and Chemotherapy)

  • Thomas Vercruysse

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network
    Translational Platform Virology and Chemotherapy)

  • Xinyu Wang

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

  • Dirk Jochmans

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

  • Erik Martens

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation)

  • Kenny Roose

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University)

  • Dorien Vlieger

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University)

  • Bert Schepens

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University)

  • Tina Buyten

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network)

  • Sofie Jacobs

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network)

  • Yanan Liu

    (Utah State University)

  • Joan Martí-Carreras

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Zoonotic Infectious Diseases Unit)

  • Bert Vanmechelen

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Zoonotic Infectious Diseases Unit)

  • Tony Wawina-Bokalanga

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Zoonotic Infectious Diseases Unit)

  • Leen Delang

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network)

  • Joana Rocha-Pereira

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network)

  • Lotte Coelmont

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

  • Winston Chiu

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network)

  • Pieter Leyssen

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network)

  • Elisabeth Heylen

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network)

  • Dominique Schols

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation)

  • Lanjiao Wang

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    GVN, Global Virus Network)

  • Lila Close

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Laboratory of Viral Metagenomics)

  • Jelle Matthijnssens

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Laboratory of Viral Metagenomics)

  • Marc Ranst

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    University Hospitals Leuven
    National Reference Center for Respiratory Pathogens and Enteroviruses
    Leuven University Vaccinology Center (LUVAC))

  • Veerle Compernolle

    (Blood Service, Belgian Red Cross Flanders
    Ghent University)

  • Georg Schramm

    (KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging and MoSAIC
    University Hospitals Leuven)

  • Koen Laere

    (KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging and MoSAIC
    University Hospitals Leuven)

  • Xavier Saelens

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University)

  • Nico Callewaert

    (VIB-UGent Center for Medical Biotechnology, VIB
    Ghent University)

  • Ghislain Opdenakker

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation)

  • Piet Maes

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Zoonotic Infectious Diseases Unit)

  • Birgit Weynand

    (KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research
    Division of Translational Cell and Tissue Research)

  • Christopher Cawthorne

    (KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging and MoSAIC)

  • Greetje Vande Velde

    (KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC)

  • Zhongde Wang

    (Utah State University)

  • Johan Neyts

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

  • Kai Dallmeier

    (Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
    Molecular Vaccinology and Vaccine Discovery Group
    GVN, Global Virus Network)

Abstract

Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

Suggested Citation

  • Robbert Boudewijns & Hendrik Jan Thibaut & Suzanne J. F. Kaptein & Rong Li & Valentijn Vergote & Laura Seldeslachts & Johan Weyenbergh & Carolien Keyzer & Lindsey Bervoets & Sapna Sharma & Laurens Lie, 2020. "STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19684-y
    DOI: 10.1038/s41467-020-19684-y
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    Citations

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

    1. Tomokazu Yamaguchi & Midori Hoshizaki & Takafumi Minato & Satoru Nirasawa & Masamitsu N. Asaka & Mayumi Niiyama & Masaki Imai & Akihiko Uda & Jasper Fuk-Woo Chan & Saori Takahashi & Jianbo An & Akari , 2021. "ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Rana Abdelnabi & Caroline S. Foo & Dirk Jochmans & Laura Vangeel & Steven De Jonghe & Patrick Augustijns & Raf Mols & Birgit Weynand & Thanaporn Wattanakul & Richard M. Hoglund & Joel Tarning & Charle, 2022. "The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 13(1), pages 1-9, 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. Sapna Sharma & Thomas Vercruysse & Lorena Sanchez-Felipe & Winnie Kerstens & Madina Rasulova & Lindsey Bervoets & Carolien Keyzer & Rana Abdelnabi & Caroline S. Foo & Viktor Lemmens & Dominique Loover, 2022. "Updated vaccine protects against SARS-CoV-2 variants including Omicron (B.1.1.529) and prevents transmission in hamsters," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Rana Abdelnabi & Dirk Jochmans & Kim Donckers & Bettina Trüeb & Nadine Ebert & Birgit Weynand & Volker Thiel & Johan Neyts, 2023. "Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in female Syrian hamsters and retains partial susceptibility to treatment," Nature Communications, Nature, vol. 14(1), pages 1-7, December.

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