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.
Bhattacharya, A., Hegazy, A. N., Deigendesch, N., Kosack, L., Cupovic, J., Kandasamy, R. K., … Bergthaler, A. (2015). Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage. Immunity, 43(5), 974–986. https://doi.org/10.1016/j.immuni.2015.10.013