Year: 2015
Type: article
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.
Source: Immunity
Authors: Anannya Bhattacharya, Ahmed N. Hegazy, Nikolaus Deigendesch, Lindsay Kosack, Jovana Cupovic, Richard K. Kandasamy, Andrea Hildebrandt, Doron Merkler, Anja A. Kühl, Bojan Vilagos, Christopher Schliehe, Isabel Panse, Kseniya Khamina, Hatoon Baazim, Isabelle Arnold, Lukas Flatz, Haifeng C. Xu, Philipp A. Lang, Alan Aderem, Akinori Takaoka, Giulio Superti-Furga, Jacques Colinge, Burkhard Ludewig, Max Löhning, Andreas Bergthaler
Institutions: Austrian Academy of Sciences, CeMM Research Center for Molecular Medicine, John Radcliffe Hospital, University of Oxford, German Rheumatism Research Centre, Charité – Universitätsmedizin Berlin, Max Planck Institute for Infection Biology, Kantonsspital St. Gallen, University of Geneva, Universitätsmedizin Göttingen, University of Göttingen, Heinrich Heine University Düsseldorf, Center for Infectious Disease Research, Hokkaido University, Institute for Genetic Medicine, Hokkaido University, Medical University of Vienna
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,812
Funders: National Science Foundation, Alexander von Humboldt-Stiftung, European Commission, Deutscher Akademischer Austauschdienst, Deutsche Forschungsgemeinschaft, Volkswagen Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Österreichischen Akademie der Wissenschaften, Bundesministerium für Bildung und Forschung, Austrian Science Fund, Universität Wien, Medizinische Universität Wien, Veterinärmedizinische Universität Wien, Japan Society for the Promotion of Science
Awards: G1263991214, G1650684859, Viral triggers and gray matter involvement in multiple sclerosis, G4662980202, G5033043955, G614235862, Regulation of Pathogenic CD4 T Cell Responses in Inflammatory Bowel Disease, G840949211, G853243261, The novel post-transcriptional regulation mechanism of antiviral host defense
OpenAlex ID: W2179216099