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DOI 10.1038/s41467-020-19684-y

Медицинская библиотека · Nature communications · 2020

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

Boudewijns Robbert, Thibaut Hendrik Jan, Kaptein Suzanne J F, Li Rong, Vergote Valentijn, Seldeslachts Laura, Van Weyenbergh Johan, De Keyzer Carolien, Bervoets Lindsey, Sharma Sapna, Liesenborghs Laurens, Ma Ji, Jansen Sander, Van Looveren Dominique, Vercruysse Thomas, Wang Xinyu, Jochmans Dirk, 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, Vande Velde Greetje, Wang Zhongde, Neyts Johan, Dallmeier Kai

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Аннотация

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.

Для цитирования: Boudewijns Robbert, Thibaut Hendrik Jan, Kaptein Suzanne J F, Li Rong, Vergote Valentijn, Seldeslachts Laura, Van Weyenbergh Johan, De Keyzer Carolien, Bervoets Lindsey, Sharma Sapna, Liesenborghs Laurens, Ma Ji, Jansen Sander, Van Looveren Dominique, Vercruysse Thomas, Wang Xinyu, Jochmans Dirk, 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, Vande Velde Greetje, Wang Zhongde, Neyts Johan, Dallmeier Kai. STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters.. Nature communications. 2020. DOI: 10.1038/s41467-020-19684-y.

Предметные рубрики MeSH

AnimalsBetacoronavirusCOVID-19Coronavirus InfectionsCricetinaeDisease Models, AnimalImmunity, InnateInterferon Type ILungMicePandemicsPneumonia, ViralSARS-CoV-2STAT2 Transcription FactorSignal TransductionVirus Replication
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