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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 Van Weyenbergh, Carolien De Keyzer, Lindsey Bervoets, Sapna Sharma, et al.
(2020) NATURE COMMUNICATIONS. 11(1).
Author
Organization
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. SARS-CoV-2 infection can result in severe lung inflammation and pathology, but host response remains incompletely understood. Here the authors show in Syrian hamsters that STAT2 signaling restricts systemic virus dissemination but also drives severe lung injury, playing a dual role in SARS-CoV-2 infection.
Keywords
General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry, RESPIRATORY SYNDROME CORONAVIRUS, SAMPLE PREPARATION PROCEDURES, MODULAR APPROACH, I INTERFERON, MICE, SARS, PATHOGENESIS, MACROPHAGES, COVID-19, MODEL

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MLA
Boudewijns, Robbert, et al. “STAT2 Signaling Restricts Viral Dissemination but Drives Severe Pneumonia in SARS-CoV-2 Infected Hamsters.” NATURE COMMUNICATIONS, vol. 11, no. 1, 2020, doi:10.1038/s41467-020-19684-y.
APA
Boudewijns, R., Thibaut, H. J., Kaptein, S. J. F., Li, R., Vergote, V., Seldeslachts, L., … Dallmeier, K. (2020). STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters. NATURE COMMUNICATIONS, 11(1). https://doi.org/10.1038/s41467-020-19684-y
Chicago author-date
Boudewijns, Robbert, Hendrik Jan Thibaut, Suzanne J. F. Kaptein, Rong Li, Valentijn Vergote, Laura Seldeslachts, Johan Van Weyenbergh, et al. 2020. “STAT2 Signaling Restricts Viral Dissemination but Drives Severe Pneumonia in SARS-CoV-2 Infected Hamsters.” NATURE COMMUNICATIONS 11 (1). https://doi.org/10.1038/s41467-020-19684-y.
Chicago author-date (all authors)
Boudewijns, Robbert, Hendrik Jan Thibaut, Suzanne J. F. Kaptein, Rong Li, Valentijn Vergote, Laura Seldeslachts, Johan Van Weyenbergh, Carolien De Keyzer, Lindsey Bervoets, Sapna Sharma, Laurens Liesenborghs, Ji Ma, Sander Jansen, Dominique Van Looveren, Thomas Vercruysse, Xinyu Wang, Dirk Jochmans, Erik Martens, Kenny Roose, Dorien De Vlieger, Bert Schepens, Tina Van 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 Van Ranst, Veerle Compernolle, Georg Schramm, Koen Van Laere, Xavier Saelens, Nico Callewaert, Ghislain Opdenakker, Piet Maes, Birgit Weynand, Christopher Cawthorne, Greetje Vande Velde, Zhongde Wang, Johan Neyts, and Kai Dallmeier. 2020. “STAT2 Signaling Restricts Viral Dissemination but Drives Severe Pneumonia in SARS-CoV-2 Infected Hamsters.” NATURE COMMUNICATIONS 11 (1). doi:10.1038/s41467-020-19684-y.
Vancouver
1.
Boudewijns R, Thibaut HJ, Kaptein SJF, Li R, Vergote V, Seldeslachts L, et al. STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters. NATURE COMMUNICATIONS. 2020;11(1).
IEEE
[1]
R. Boudewijns et al., “STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters,” NATURE COMMUNICATIONS, vol. 11, no. 1, 2020.
@article{8685063,
  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. SARS-CoV-2 infection can result in severe lung inflammation and pathology, but host response remains incompletely understood. Here the authors show in Syrian hamsters that STAT2 signaling restricts systemic virus dissemination but also drives severe lung injury, playing a dual role in SARS-CoV-2 infection.}},
  articleno    = {{5838}},
  author       = {{Boudewijns, Robbert and Thibaut, Hendrik Jan and Kaptein, Suzanne J. F. and Li, Rong and Vergote, Valentijn and Seldeslachts, Laura and Van Weyenbergh, Johan and De Keyzer, Carolien and Bervoets, Lindsey and Sharma, Sapna and Liesenborghs, Laurens and Ma, Ji and Jansen, Sander and Van Looveren, Dominique and Vercruysse, Thomas and Wang, Xinyu and Jochmans, Dirk and Martens, Erik and Roose, Kenny and De Vlieger, Dorien and Schepens, Bert and Van Buyten, Tina and Jacobs, Sofie and Liu, Yanan and Martí-Carreras, Joan and Vanmechelen, Bert and Wawina-Bokalanga, Tony and Delang, Leen and Rocha-Pereira, Joana and Coelmont, Lotte and Chiu, Winston and Leyssen, Pieter and Heylen, Elisabeth and Schols, Dominique and Wang, Lanjiao and Close, Lila and Matthijnssens, Jelle and Van Ranst, Marc and Compernolle, Veerle and Schramm, Georg and Van Laere, Koen and Saelens, Xavier and Callewaert, Nico and Opdenakker, Ghislain and Maes, Piet and Weynand, Birgit and Cawthorne, Christopher and Vande Velde, Greetje and Wang, Zhongde and Neyts, Johan and Dallmeier, Kai}},
  issn         = {{2041-1723}},
  journal      = {{NATURE COMMUNICATIONS}},
  keywords     = {{General Biochemistry,Genetics and Molecular Biology,General Physics and Astronomy,General Chemistry,RESPIRATORY SYNDROME CORONAVIRUS,SAMPLE PREPARATION PROCEDURES,MODULAR APPROACH,I INTERFERON,MICE,SARS,PATHOGENESIS,MACROPHAGES,COVID-19,MODEL}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{10}},
  title        = {{STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters}},
  url          = {{http://doi.org/10.1038/s41467-020-19684-y}},
  volume       = {{11}},
  year         = {{2020}},
}
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