Epidermal growth factor receptor signaling impairs the antiviral activity of interferon-alpha

摘要: Interferon-alpha (IFN-alpha) exhibits its antiviral activity through signal transducer and activator of transcription protein (STAT) signaling the expression IFN response genes (IRGs). Viral infection has been shown to result in activation epidermal growth factor receptor (EGFR)-a host cell entry used by several viruses, including hepatitis C virus. However, effect EGFR for cellular responses is unknown. Here, we uncover cross-talk between IFN-alpha that a therapeutic on IFN-alpha-based therapies functional relevance viral evasion resistance. We show combining with inhibitor, erlotinib, potentiates each compound highly synergistic manner. The extent synergy correlated reduced STAT3 phosphorylation presence whereas STAT1 was not affected. Furthermore, enhanced suppressors cytokine 3 (SOCS3) erlotinib IRGs, radical S-adenosyl methionine domain containing 2 myxovirus resistance 1. Moreover, stimulation dimerization, but phosphorylation, indicating acts STATs at level binding DNA. Conclusions: Our results support model where inhibition impairs leading IRG activity. These data novel role open new avenues improving efficacy therapies.