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

Animals Betacoronavirus / pathogenicity COVID-19 Coronavirus Infections / immunology Cricetinae Disease Models, Animal Immunity, Innate Interferon Type I / genetics Lung / pathology Mice Pandemics Pneumonia, Viral / immunology SARS-CoV-2 STAT2 Transcription Factor / genetics Signal Transduction Virus Replication

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
17 11 2020
Historique:
received: 18 09 2020
accepted: 27 10 2020
entrez: 18 11 2020
pubmed: 19 11 2020
medline: 1 12 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-19684-y PMID: 33203860 PMC: PMC7672082
pubmed: 33203860
doi: 10.1038/s41467-020-19684-y
pii: 10.1038/s41467-020-19684-y
pmc: PMC7672082
doi:

Substances chimiques

Interferon Type I 0
STAT2 Transcription Factor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5838

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom

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Auteurs

Robbert Boudewijns (R)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
ORCID: 0000-0002-5984-7279

Hendrik Jan Thibaut (HJ)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.
GVN, Global Virus Network, Baltimore, MD, USA. hendrikjan.thibaut@kuleuven.be.
Translational Platform Virology and Chemotherapy, Leuven, Belgium. hendrikjan.thibaut@kuleuven.be.
ORCID: 0000-0001-5785-8276

Suzanne J F Kaptein (SJF)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
ORCID: 0000-0002-7935-0219

Rong Li (R)

Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, 84322-4815, USA.

Valentijn Vergote (V)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Zoonotic Infectious Diseases Unit, Leuven, Belgium.
ORCID: 0000-0002-4436-3212

Laura Seldeslachts (L)

KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC, 3000, Leuven, Belgium.

Johan Van Weyenbergh (J)

Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.

Carolien De Keyzer (C)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.

Lindsey Bervoets (L)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.

Sapna Sharma (S)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
ORCID: 0000-0003-3493-252X

Laurens Liesenborghs (L)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
ORCID: 0000-0001-5616-8548

Ji Ma (J)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.

Sander Jansen (S)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
ORCID: 0000-0002-9344-131X

Dominique Van Looveren (D)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
Translational Platform Virology and Chemotherapy, Leuven, Belgium.

Thomas Vercruysse (T)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
Translational Platform Virology and Chemotherapy, Leuven, Belgium.

Xinyu Wang (X)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.

Dirk Jochmans (D)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
ORCID: 0000-0002-9265-6028

Erik Martens (E)

Immunity and Inflammation Research Group, Immunobiology Unit, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.

Kenny Roose (K)

VIB-UGent Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium.
Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium.
ORCID: 0000-0002-5270-4603

Dorien De Vlieger (D)

VIB-UGent Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium.
Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium.

Bert Schepens (B)

VIB-UGent Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium.
Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium.

Tina Van Buyten (T)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.

Sofie Jacobs (S)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
ORCID: 0000-0001-8657-6841

Yanan Liu (Y)

Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, 84322-4815, USA.

Joan Martí-Carreras (J)

Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Zoonotic Infectious Diseases Unit, Leuven, Belgium.
ORCID: 0000-0002-0005-9761

Bert Vanmechelen (B)

Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Zoonotic Infectious Diseases Unit, Leuven, Belgium.
ORCID: 0000-0002-8350-4356

Tony Wawina-Bokalanga (T)

Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Zoonotic Infectious Diseases Unit, Leuven, Belgium.

Leen Delang (L)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
ORCID: 0000-0002-8874-675X

Joana Rocha-Pereira (J)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.

Lotte Coelmont (L)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.

Winston Chiu (W)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
ORCID: 0000-0001-5236-623X

Pieter Leyssen (P)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.

Elisabeth Heylen (E)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.
ORCID: 0000-0003-4359-7225

Dominique Schols (D)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.

Lanjiao Wang (L)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
GVN, Global Virus Network, Baltimore, MD, USA.

Lila Close (L)

Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Laboratory of Viral Metagenomics, Leuven, Belgium.

Jelle Matthijnssens (J)

Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Laboratory of Viral Metagenomics, Leuven, Belgium.
ORCID: 0000-0003-1188-9733

Marc Van Ranst (M)

Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
KU Leuven Department of Laboratory Medicine, University Hospitals Leuven, 3000, Leuven, Belgium.
National Reference Center for Respiratory Pathogens and Enteroviruses, 3000, Leuven, Belgium.
Leuven University Vaccinology Center (LUVAC), 3000, Leuven, Belgium.

Veerle Compernolle (V)

Blood Service, Belgian Red Cross Flanders, Mechelen, Belgium.
Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.

Georg Schramm (G)

KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging and MoSAIC, 3000, Leuven, Belgium.
Division of Nuclear Medicine, University Hospitals Leuven, 3000, Leuven, Belgium.
ORCID: 0000-0002-2251-3195

Koen Van Laere (K)

KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging and MoSAIC, 3000, Leuven, Belgium.
Division of Nuclear Medicine, University Hospitals Leuven, 3000, Leuven, Belgium.
ORCID: 0000-0001-5200-7245

Xavier Saelens (X)

VIB-UGent Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium.
Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium.
ORCID: 0000-0002-3861-6965

Nico Callewaert (N)

VIB-UGent Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium.
Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium.
ORCID: 0000-0003-2069-6917

Ghislain Opdenakker (G)

Immunity and Inflammation Research Group, Immunobiology Unit, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
ORCID: 0000-0003-1714-2294

Piet Maes (P)

Laboratory of Clinical and Epidemiological Virology, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.
Zoonotic Infectious Diseases Unit, Leuven, Belgium.
ORCID: 0000-0002-4571-5232

Birgit Weynand (B)

KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, 3000, Leuven, Belgium.
Division of Translational Cell and Tissue Research, Leuven, Belgium.
ORCID: 0000-0003-4246-6303

Christopher Cawthorne (C)

KU Leuven Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging and MoSAIC, 3000, Leuven, Belgium.
ORCID: 0000-0002-5975-0354

Greetje Vande Velde (G)

KU Leuven Department of Imaging and Pathology, Biomedical MRI and MoSAIC, 3000, Leuven, Belgium.
ORCID: 0000-0002-5633-3993

Zhongde Wang (Z)

Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, 84322-4815, USA.
ORCID: 0000-0003-2441-4729

Johan Neyts (J)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium. johan.neyts@kuleuven.be.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium. johan.neyts@kuleuven.be.
GVN, Global Virus Network, Baltimore, MD, USA. johan.neyts@kuleuven.be.
ORCID: 0000-0002-0033-7514

Kai Dallmeier (K)

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium. kai.dallmeier@kuleuven.be.
Molecular Vaccinology and Vaccine Discovery Group, Leuven, Belgium. kai.dallmeier@kuleuven.be.
GVN, Global Virus Network, Baltimore, MD, USA. kai.dallmeier@kuleuven.be.
ORCID: 0000-0002-8117-9166

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Infection › Maladies virales › Infections à virus à ARN › Infections à Nidovirales › Infections à Coronaviridae › Infections à coronavirus › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Arvicolinae › Cricetinae › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité innée › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Interféron de type I › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Appareil respiratoire › Poumon › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Épidémies de maladies › Épidémies › Pandémies › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription STAT › Facteur de transcription STAT-2 › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › STAT2 signaling restricts viral dissemination...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › STAT2 signaling restricts viral dissemination...