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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. 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. Viral infection leads to redox dysregulation including the downregulation of SOD1. Bergthaler and colleagues show that superoxide dismutase 1 protects the liver from type I interferon-driven oxidative damage in viral hepatitis.
These viral infections often lead to liver damage and associated complications such as advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma, which cause substantial morbidity and mortality Guidotti and Chisari, , Park and Rehermann, The complex pathology of viral hepatitis is driven by multiple viral and host factors interacting with various immune cell populations and cytokines such as type I interferon-I IFN-I Park and Rehermann, , Schoggins et al.
Together, these determinants mediate the antiviral response, but they also lead to subsequent immunopathology and tissue damage Guidotti and Chisari, , Medzhitov et al. Yet, the mechanisms involved are largely unknown.
