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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.
  • Boudewijns R; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Thibaut HJ; Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
  • Kaptein SJF; GVN, Global Virus Network, Baltimore, MD, USA.
  • Li R; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.
  • Vergote V; GVN, Global Virus Network, Baltimore, MD, USA. hendrikjan.thibaut@kuleuven.be.
  • Seldeslachts L; Translational Platform Virology and Chemotherapy, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.
  • Van Weyenbergh J; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • De Keyzer C; GVN, Global Virus Network, Baltimore, MD, USA.
  • Bervoets L; Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, 84322-4815, USA.
  • Sharma S; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Liesenborghs L; Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Ma J; Zoonotic Infectious Diseases Unit, Leuven, Belgium.
  • Jansen S; KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC, 3000, Leuven, Belgium.
  • Van Looveren D; Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Vercruysse T; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Wang X; Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
  • Jochmans D; GVN, Global Virus Network, Baltimore, MD, USA.
  • Martens E; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Roose K; GVN, Global Virus Network, Baltimore, MD, USA.
  • De Vlieger D; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Schepens B; Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
  • Van Buyten T; GVN, Global Virus Network, Baltimore, MD, USA.
  • Jacobs S; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Liu Y; Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
  • Martí-Carreras J; GVN, Global Virus Network, Baltimore, MD, USA.
  • Vanmechelen B; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Wawina-Bokalanga T; Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
  • Delang L; GVN, Global Virus Network, Baltimore, MD, USA.
  • Rocha-Pereira J; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Coelmont L; Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
  • Chiu W; GVN, Global Virus Network, Baltimore, MD, USA.
  • Leyssen P; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Heylen E; GVN, Global Virus Network, Baltimore, MD, USA.
  • Schols D; Translational Platform Virology and Chemotherapy, Leuven, Belgium.
  • Wang L; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Close L; GVN, Global Virus Network, Baltimore, MD, USA.
  • Matthijnssens J; Translational Platform Virology and Chemotherapy, Leuven, Belgium.
  • Van Ranst M; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Compernolle V; Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
  • Schramm G; GVN, Global Virus Network, Baltimore, MD, USA.
  • Van Laere K; Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Saelens X; Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
  • Callewaert N; GVN, Global Virus Network, Baltimore, MD, USA.
  • Opdenakker G; Immunity and Inflammation Research Group, Immunobiology Unit, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
  • Maes P; VIB-UGent Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium.
  • Weynand B; Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium.
  • Cawthorne C; VIB-UGent Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium.
  • Vande Velde G; Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium.
  • Wang Z; VIB-UGent Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium.
  • Neyts J; Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium.
Nat Commun ; 11(1): 5838, 2020 11 17.
Artículo en Inglés | MEDLINE | ID: covidwho-933686
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.
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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Neumonía Viral / Transducción de Señal / Infecciones por Coronavirus / Modelos Animales de Enfermedad / Factor de Transcripción STAT2 / Betacoronavirus Tipo de estudio: Estudio pronóstico Límite: Animales Idioma: Inglés Revista: Nat Commun Asunto de la revista: Biologia / Ciencia Año: 2020 Tipo del documento: Artículo País de afiliación: S41467-020-19684-y

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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Neumonía Viral / Transducción de Señal / Infecciones por Coronavirus / Modelos Animales de Enfermedad / Factor de Transcripción STAT2 / Betacoronavirus Tipo de estudio: Estudio pronóstico Límite: Animales Idioma: Inglés Revista: Nat Commun Asunto de la revista: Biologia / Ciencia Año: 2020 Tipo del documento: Artículo País de afiliación: S41467-020-19684-y