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

Robbert Boudewijns(Rega Institute for Medical Research), Hendrik Jan Thibaut(Rega Institute for Medical Research), Suzanne J. F. Kaptein(Rega Institute for Medical Research), Rong Li(Utah State University), Valentijn Vergote(Rega Institute for Medical Research), Laura Seldeslachts(KU Leuven), Johan Van Weyenbergh(Rega Institute for Medical Research), Carolien De Keyzer(Rega Institute for Medical Research), Lindsey Bervoets(Rega Institute for Medical Research), Sapna Sharma(Rega Institute for Medical Research), Laurens Liesenborghs(Rega Institute for Medical Research), Ji Ma(Rega Institute for Medical Research), Sander Jansen(Rega Institute for Medical Research), Dominique Van Looveren(Rega Institute for Medical Research), Thomas Vercruysse(Rega Institute for Medical Research), Xinyu Wang(Rega Institute for Medical Research), Dirk Jochmans(Rega Institute for Medical Research), Erik Martens(Rega Institute for Medical Research), Kenny Roose(Ghent University), Dorien De Vlieger(Ghent University), Bert Schepens(Ghent University), Tina Van Buyten(Rega Institute for Medical Research), Sofie Jacobs(Rega Institute for Medical Research), Yanan Liu(Utah State University), Joan Martí‐Carreras(Rega Institute for Medical Research), Bert Vanmechelen(Rega Institute for Medical Research), Tony Wawina-Bokalanga(Rega Institute for Medical Research), Leen Delang(Rega Institute for Medical Research), Joana Rocha‐Pereira(Rega Institute for Medical Research), Lotte Coelmont(Rega Institute for Medical Research), Winston Chiu(Rega Institute for Medical Research), Pieter Leyssen(Rega Institute for Medical Research), Elisabeth Heylen(Rega Institute for Medical Research), Dominique Schols(Rega Institute for Medical Research), Lanjiao Wang(Rega Institute for Medical Research), Lila Close(Rega Institute for Medical Research), Jelle Matthijnssens(Rega Institute for Medical Research), Marc Van Ranst(European Union), Veerle Compernolle(Ghent University), Georg Schramm(KU Leuven), Koen Van Laere(KU Leuven), Xavier Saelens(Ghent University), Nico Callewaert(Ghent University), Ghislain Opdenakker(Rega Institute for Medical Research), Piet Maes(Rega Institute for Medical Research), Birgit Weynand(KU Leuven), Christopher Cawthorne(KU Leuven), Greetje Vande Velde(KU Leuven), Zhongde Wang(Utah State University), Johan Neyts(Rega Institute for Medical Research), Kai Dallmeier(Rega Institute for Medical Research)
Nature Communications
November 17, 2020
10.1038/s41467-020-19684-y
Cited by 292Open Access
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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.

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