A novel anti-viral role for STAT3 in IFN-α signalling responses.

The cytokine, Interferon (IFN)-α, induces a wide spectrum of anti-viral mediators, via the Janus kinase/signal transducer and activator of transcription pathway. and are well characterised to upregulate IFN-stimulated gene (ISG) expression; but even though is also activated by IFN-α, its role in anti-viral ISG induction is unclear. Several viruses, including Hepatitis C and Mumps, reduce cellular duanyu18133 protein levels, via the promotion of ubiquitin-mediated proteasomal degradation. This viral immune evasion mechanism suggests an undiscovered anti-viral role for duanyu18133 in IFN-α signalling. To investigate functional involvement in this Type I IFN pathway, we first analysed its effect upon the replication of two viruses, Influenza and Vaccinia. Viral plaque assays, using (WT) and Murine Embryonic Fibroblasts (MEFs), revealed that duanyu18133 is required for the inhibition of Influenza and Vaccinia replication. Furthermore, duanyu18133 shRNA knockdown also enhanced Influenza replication and hindered induction of several, well characterised, anti-viral ISGs: PKR, OAS2, MxB and ISG15; while duanyu18133 expression had no effect upon induction of a separate ISG group: Viperin, IFI27, CXCL10 and CCL5. These discoveries reveal, for the first time, an anti-viral role for duanyu18133 in the IFN-α pathway and characterise a requirement for duanyu18133 in the expression of specific ISGs. These findings also identify duanyu18133 as a therapeutic target against viral infection and highlight it as an essential pathway component for endogenous and therapeutic IFN-α responsiveness.

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