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

Robbert Boudewijns, Hendrik Jan Thibaut (), Suzanne J. F. Kaptein, Rong Li, Valentijn Vergote, Laura Seldeslachts, Johan Weyenbergh, Carolien Keyzer, Lindsey Bervoets, Sapna Sharma, Laurens Liesenborghs, Ji Ma, Sander Jansen, Dominique Looveren, Thomas Vercruysse, Xinyu Wang, Dirk Jochmans, Erik Martens, Kenny Roose, Dorien Vlieger, Bert Schepens, Tina Buyten, Sofie Jacobs, Yanan Liu, Joan Martí-Carreras, Bert Vanmechelen, Tony Wawina-Bokalanga, Leen Delang, Joana Rocha-Pereira, Lotte Coelmont, Winston Chiu, Pieter Leyssen, Elisabeth Heylen, Dominique Schols, Lanjiao Wang, Lila Close, Jelle Matthijnssens, Marc Ranst, Veerle Compernolle, Georg Schramm, Koen Laere, Xavier Saelens, Nico Callewaert, Ghislain Opdenakker, Piet Maes, Birgit Weynand, Christopher Cawthorne, Greetje Vande Velde, Zhongde Wang, Johan Neyts () and Kai Dallmeier ()
Additional contact information
Robbert Boudewijns: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Hendrik Jan Thibaut: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Suzanne J. F. Kaptein: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Rong Li: Utah State University
Valentijn Vergote: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
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
Lindsey Bervoets: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Sapna Sharma: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Laurens Liesenborghs: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Ji Ma: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Sander Jansen: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Dominique Looveren: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Thomas Vercruysse: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Xinyu Wang: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Dirk Jochmans: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Erik Martens: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Kenny Roose: VIB-UGent Center for Medical Biotechnology, VIB
Dorien Vlieger: VIB-UGent Center for Medical Biotechnology, VIB
Bert Schepens: VIB-UGent Center for Medical Biotechnology, VIB
Tina Buyten: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Sofie Jacobs: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Yanan Liu: Utah State University
Joan Martí-Carreras: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Bert Vanmechelen: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Tony Wawina-Bokalanga: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Leen Delang: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Joana Rocha-Pereira: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Lotte Coelmont: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Winston Chiu: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Pieter Leyssen: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Elisabeth Heylen: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Dominique Schols: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Lanjiao Wang: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Lila Close: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Jelle Matthijnssens: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Marc Ranst: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Veerle Compernolle: Blood Service, Belgian Red Cross Flanders
Georg Schramm: KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging and MoSAIC
Koen Laere: KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging and MoSAIC
Xavier Saelens: VIB-UGent Center for Medical Biotechnology, VIB
Nico Callewaert: VIB-UGent Center for Medical Biotechnology, VIB
Ghislain Opdenakker: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Piet Maes: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation
Birgit Weynand: KU Leuven Department of Imaging and Pathology, 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
Kai Dallmeier: Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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.

Date: 2020
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Citations: View citations in EconPapers (5)

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DOI: 10.1038/s41467-020-19684-y

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