STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters
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Published:2020-11-17
Issue:1
Volume:11
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Boudewijns RobbertORCID, Thibaut Hendrik JanORCID, Kaptein Suzanne J. F.ORCID, Li Rong, Vergote ValentijnORCID, Seldeslachts Laura, Van Weyenbergh Johan, De Keyzer Carolien, Bervoets Lindsey, Sharma SapnaORCID, Liesenborghs LaurensORCID, Ma Ji, Jansen SanderORCID, Van Looveren Dominique, Vercruysse Thomas, Wang Xinyu, Jochmans DirkORCID, Martens Erik, Roose KennyORCID, De Vlieger Dorien, Schepens Bert, Van Buyten Tina, Jacobs SofieORCID, Liu Yanan, Martí-Carreras JoanORCID, Vanmechelen BertORCID, Wawina-Bokalanga Tony, Delang LeenORCID, Rocha-Pereira Joana, Coelmont Lotte, Chiu WinstonORCID, Leyssen Pieter, Heylen ElisabethORCID, Schols Dominique, Wang Lanjiao, Close Lila, Matthijnssens JelleORCID, Van Ranst Marc, Compernolle Veerle, Schramm GeorgORCID, Van Laere KoenORCID, Saelens XavierORCID, Callewaert NicoORCID, Opdenakker GhislainORCID, Maes PietORCID, Weynand BirgitORCID, Cawthorne ChristopherORCID, Vande Velde GreetjeORCID, Wang ZhongdeORCID, Neyts JohanORCID, Dallmeier KaiORCID
Abstract
AbstractEmergence 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.
Funder
EC | Horizon 2020 Framework Programme Bill and Melinda Gates Foundation Fonds Wetenschappelijk Onderzoek Hercules Foundation
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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