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

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.

SUBMITTER: Boudewijns R 

PROVIDER: S-EPMC7672082 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Boudewijns Robbert R   Thibaut Hendrik Jan HJ   Kaptein Suzanne J F SJF   Li Rong R   Vergote Valentijn V   Seldeslachts Laura L   Van Weyenbergh Johan J   De Keyzer Carolien C   Bervoets Lindsey L   Sharma Sapna S   Liesenborghs Laurens L   Ma Ji J   Jansen Sander S   Van Looveren Dominique D   Vercruysse Thomas T   Wang Xinyu X   Jochmans Dirk D   Martens Erik E   Roose Kenny K   De Vlieger Dorien D   Schepens Bert B   Van Buyten Tina T   Jacobs Sofie S   Liu Yanan Y   Martí-Carreras Joan J   Vanmechelen Bert B   Wawina-Bokalanga Tony T   Delang Leen L   Rocha-Pereira Joana J   Coelmont Lotte L   Chiu Winston W   Leyssen Pieter P   Heylen Elisabeth E   Schols Dominique D   Wang Lanjiao L   Close Lila L   Matthijnssens Jelle J   Van Ranst Marc M   Compernolle Veerle V   Schramm Georg G   Van Laere Koen K   Saelens Xavier X   Callewaert Nico N   Opdenakker Ghislain G   Maes Piet P   Weynand Birgit B   Cawthorne Christopher C   Vande Velde Greetje G   Wang Zhongde Z   Neyts Johan J   Dallmeier Kai K  

Nature communications 20201117 1

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  ...[more]

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