title: Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage.
abstract: Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1(-/-) mice exhibited increased inflammation and aggravated liver damage upon viral infection, which was independent of T and NK cells and could be ameliorated by antioxidant treatment. Type I interferon (IFN-I) led to a downregulation of Sod1 and caused oxidative liver damage in Sod1(-/-) and wild-type mice. Genetic and pharmacological ablation of the IFN-I signaling pathway protected against virus-induced liver damage. These results delineate IFN-I mediated oxidative stress as a key mediator of virus-induced liver damage and describe a mechanism of innate-immunity-driven pathology, linking IFN-I signaling with antioxidant host defense and infection-associated tissue damage. VIDEO ABSTRACT.
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria.
authors.forename: Anannya
authors.initials: A
authors.lastname: Bhattacharya
authors.affiliation: Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; German Rheumatism Research Center (DRFZ), a Leibniz Institute, 10117 Berlin, Germany; Translational Gastroenterology Unit, Experimental Medicine Division Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, OX3 9DU Oxford, UK.
authors.forename: Ahmed N
authors.initials: AN
authors.lastname: Hegazy
authors.affiliation: Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Deigendesch
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Kosack
authors.affiliation: Institute of Immunobiology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007 St. Gallen, Switzerland.
authors.forename: Jovana
authors.initials: J
authors.lastname: Cupovic
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Kandasamy
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hildebrandt
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Geneva, Switzerland; Department of Neuropathology, University Medicine Göttingen, Robert-Koch Strasse 40, 37099 Goettingen, Germany.
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.affiliation: Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200 Berlin, Germany.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria.
authors.forename: Bojan
authors.initials: B
authors.lastname: Vilagos
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria.
authors.forename: Christopher
authors.initials: C
authors.lastname: Schliehe
authors.affiliation: Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; German Rheumatism Research Center (DRFZ), a Leibniz Institute, 10117 Berlin, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Panse
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria.
authors.forename: Kseniya
authors.initials: K
authors.lastname: Khamina
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria.
authors.forename: Hatoon
authors.initials: H
authors.lastname: Baazim
authors.affiliation: Translational Gastroenterology Unit, Experimental Medicine Division Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, OX3 9DU Oxford, UK.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Arnold
authors.affiliation: Institute of Immunobiology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007 St. Gallen, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Flatz
authors.affiliation: Department of Gastroenterology, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors.forename: Haifeng C
authors.initials: HC
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany; Department of Molecular Medicine II, Heinrich Heine University, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109-5219, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.affiliation: Division of Signaling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Takaoka
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria; Center for Physiology and Pharmacology, Medical University of Vienna, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: Giulio
authors.initials: G
authors.lastname: Superti-Furga
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria.
authors.forename: Jacques
authors.initials: J
authors.lastname: Colinge
authors.affiliation: Institute of Immunobiology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007 St. Gallen, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.affiliation: Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; German Rheumatism Research Center (DRFZ), a Leibniz Institute, 10117 Berlin, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Löhning
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT25.3, 1090 Vienna, Austria. Electronic address: abergthaler@cemm.oeaw.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergthaler
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D006524:Hepatitis, Viral, Animal / Q000276:immunology; D022781:Hepatocytes / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013482:Superoxide Dismutase / Q000276:immunology*; D000072105:Superoxide Dismutase-1; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D000975:Antioxidants; D007370:Interferon Type I; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1