Author: Boudewijns, Robbert; Thibaut, Hendrik Jan; Kaptein, Suzanne J. F.; Li, Rong; Vergote, Valentijn; Seldeslachts, Laura; De Keyzer, Carolien; Bervoets, Lindsey; Sharma, Sapna; Van Weyenbergh, Johan; Liesenborghs, Laurens; Ma, Ji; Jansen, Sander; Van Looveren, Dominique; Vercruysse, Thomas; Jochmans, Dirk; Wang, Xinyu; Martens, Erik; Roose, Kenny; De Vlieger, Dorien; Schepens, Bert; Van Buyten, Tina; Jacobs, Sofie; Liu, Yanan; MartÃ-Carreras, Joan; Vanmechelen, Bert; Wawina-Bokalanga, Tony; Delang, Leen; Rocha-Pereira, Joana; Coelmont, Lotte; Chiu, Winston; Leyssen, Pieter; Heylen, Elisabeth; Schols, Dominique; Wang, Lanjiao; Close, Lila; Matthijnssens, Jelle; Van Ranst, Marc; Compernolle, Veerle; Schramm, Georg; Van Laere, Koen; Saelens, Xavier; Callewaert, Nico; Opdenakker, Ghislain; Maes, Piet; Weynand, Birgit; Cawthorne, Christopher; Velde, Greetje Vande; Wang, Zhongde; Neyts, Johan; Dallmeier, Kai
Title: STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters Cord-id: m5u6ryy9 Document date: 2020_7_2
ID: m5u6ryy9
Snippet: Since the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and 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 productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and
Document: Since the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and 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 productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and develop bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. Moreover, we identify an exuberant innate immune response as a 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. Finally, we assess SARS-CoV- 2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. 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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