STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters

STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters

Introductory paragraph 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 nee...

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Veröffentlicht in:bioRxiv 2020
Hauptverfasser: Boudewijns, Robbert, Thibaut, Hendrik Jan, Kaptein, Suzanne, 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, Martí-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
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Sprache:eng
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Zusammenfassung:Introductory paragraph 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.