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A role for IRF3-dependent RXRalpha repression in hepatotoxicity associated with viral infections.

ABSTRACT: 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 alpha (RXRalpha) 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 RXRalpha as a molecular mechanism for pathogen-associated metabolic diseases.

SUBMITTER: Chow EK

PROVIDER: S-EPMC2118146 | biostudies-other | 2006 Nov

REPOSITORIES: biostudies-other

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A role for IRF3-dependent RXRalpha repression in hepatotoxicity associated with viral infections.

Chow Edward K EK Castrillo Antonio A Shahangian Arash A Pei Liming L O'Connell Ryan M RM Modlin Robert L RL Tontonoz Peter P Cheng Genhong G

The Journal of experimental medicine 20061030 12

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 alpha (RXRalpha) and suppresses the induction of its downstream target genes, including those involved in hepatic detoxification. Activation ...[more]

PMID: 17074929

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