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

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

Syrian hamsters are highly permissive to SARS-CoV-2. They develop severe lung disease, and are an animal model for severe COVID-19. Boudewijns et al. show that a dysregulated innate immune response is a driving force behind the severe pathogenesis in these hamsters. Signal transducer and activator of transcription factor 2 (STAT2)-dependent type I and III IFN signaling plays a dual role: (i) restricting infection and dissemination on one hand but (ii) driving development of severe lung disease on the other.

Published November 2020 in Nature Communications