A role for IRF3-dependent RXRα repression in hepatotoxicity associated with viral infections
Copyright policy )A role for IRF3-dependent RXRα repression in hepatotoxicity associated with viral infections
Viral infections and antiviral responses have been linked to several metabolic diseases, including Reye's syndrome, which is aspirin-induced hepatotoxicity in the context of a viral infection. We identify an interferon regulatory factor 3 (IRF3)–dependent but type I interferon–independent pathway that strongly inhibits the expression of retinoid X receptor α (RXRα) and suppresses the induction of its downstream target genes, including those involved in hepatic detoxification. Activation of IRF3 by viral infection in vivo greatly enhances bile acid– and aspirin-induced hepatotoxicity. Our results provide a critical link between the innate immune response and host metabolism, identifying IRF3-mediated down-regulation of RXRα as a molecular mechanism for pathogen-associated metabolic diseases.
- University of California System United States
- UCLA Jonsson Comprehensive Cancer Center United States
- University of California Los Angeles
- Institute of Molecular Biology Germany
- Howard Hughes Medical Institute United States
Gene Expression Regulation, Viral, Cells, Knockout, Chronic Liver Disease and Cirrhosis, Immunology, 610, Down-Regulation, Medical and Health Sciences, Vesicular stomatitis Indiana virus, Hepatitis, Vaccine Related, Mice, Biodefense, Rhabdoviridae Infections, 616, Genetics, 2.1 Biological and endogenous factors, Animals, Viral, Aetiology, Cells, Cultured, Mice, Knockout, Cultured, Retinoid X Receptor alpha, Animal, Prevention, Liver Disease, Reye Syndrome, Articles, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, Gene Expression Regulation, Hepatitis, Viral, Animal, Interferon Regulatory Factor-3, Digestive Diseases, Infection
Gene Expression Regulation, Viral, Cells, Knockout, Chronic Liver Disease and Cirrhosis, Immunology, 610, Down-Regulation, Medical and Health Sciences, Vesicular stomatitis Indiana virus, Hepatitis, Vaccine Related, Mice, Biodefense, Rhabdoviridae Infections, 616, Genetics, 2.1 Biological and endogenous factors, Animals, Viral, Aetiology, Cells, Cultured, Mice, Knockout, Cultured, Retinoid X Receptor alpha, Animal, Prevention, Liver Disease, Reye Syndrome, Articles, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, Gene Expression Regulation, Hepatitis, Viral, Animal, Interferon Regulatory Factor-3, Digestive Diseases, Infection
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