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

Boudewijns, R; Thibaut, HJ; Kaptein, SJF; Li, R; Vergote, V; Seldeslachts, L; Van Weyenbergh, J; De Keyzer, C; Bervoets, L; Sharma, S; Liesenborghs, L; Ma, J; Jansen, S; Van Looveren, D; Vercruysse, T; Wang, X; Jochmans, D; Martens, E; Roose, K; De Vlieger, D; Schepens, B; Van Buyten, T; Jacobs, S; Liu, Y; MARTI CARRERAS, J; Vanmechelen, B; Wawina, Tony; Delang, L; Rocha-Pereira, J; Coelmont, L; Chiu, Ju Hang Winston; Leyssen, P; Heylen, E; Schols, D; Wang, L; Close, L; Matthijnssens, J; Van Ranst, M; Compernolle, V; Schramm, G; Van Laere, K; Saelens, X; Callewaert, N; Opdenakker, G; Maes, P; Weynand, B; Cawthorne, C; Vande Velde, G; Wang, Z; Neyts, J; Dallmeier, K

doi:10.1038/s41467-020-19684-y

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

Author:

Boudewijns, R

Thibaut, HJ ; Kaptein, SJF ; Li, R ; Vergote, V ; Seldeslachts, L ; Van Weyenbergh, J ; De Keyzer, C ; Bervoets, L ; Sharma, S ; Liesenborghs, L ; Ma, J ; Jansen, S ; Van Looveren, D ; Vercruysse, T ; Wang, X ; Jochmans, D ; Martens, E ; Roose, K ; De Vlieger, D ; Schepens, B ; Van Buyten, T ; Jacobs, S ; Liu, Y ; MARTI CARRERAS, J ; Vanmechelen, B ; Wawina, Tony ; Delang, L ; Rocha-Pereira, J ; Coelmont, L ; Chiu, Ju Hang Winston ; Leyssen, P ; Heylen, E ; Schols, D ; Wang, L ; Close, L ; Matthijnssens, J ; Van Ranst, M ; Compernolle, V ; Schramm, G ; Van Laere, K ; Saelens, X ; Callewaert, N ; Opdenakker, G ; Maes, P ; Weynand, B ; Cawthorne, C ; Vande Velde, G ; Wang, Z ; Neyts, J ; Dallmeier, K

Keywords:

Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, RESPIRATORY SYNDROME CORONAVIRUS, SAMPLE PREPARATION PROCEDURES, MODULAR APPROACH, I INTERFERON, MICE, SARS, COVID-19, PATHOGENESIS, MACROPHAGES, MODEL, Animals, Betacoronavirus, Coronavirus Infections, Cricetinae, Disease Models, Animal, Immunity, Innate, Interferon Type I, Lung, Mice, Pandemics, Pneumonia, Viral, SARS-CoV-2, STAT2 Transcription Factor, Signal Transduction, Virus Replication, C24/17/061#54270844, C16/17/010#54271312, 1S28617N#54047531

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.