Differential Transcriptional Responses to Interferon-α and Interferon-γ in Primary Human Hepatocytes

Abstract

Interferon (IFN) plays a central role in the innate and adaptive antiviral immune responses. While IFN-alpha is currently approved for treating chronic hepatitis B and hepatitis C, in limited studies, IFN-gamma has not been shown to be effective for chronic hepatitis B or C. To identify the potential mechanism underlying the differential antiviral effects of IFN-alpha and IFN-gamma, we used cDNA microarray to profile the global transcriptional response to IFN-alpha and IFN-gamma in primary human hepatocytes, the target cell population of hepatitis viruses. Our results reveal distinct patterns of gene expression induced by these 2 cytokines. Overall, IFN-alpha induces more genes than IFN-gamma at the transcriptional level. Distinct sets of genes were induced by IFN-alpha and IFN-gamma with limited overlaps. IFN-alpha induces gene transcription at an early time point (6 h) but not at a later time point (18 h), while the effects of IFN-gamma are more prominent at 18 h than at 6 h, suggesting a delayed transcriptional response to IFN-gamma in the hepatocytes. These findings indicate differential actions of IFN-alpha and IFN-gamma in the context of therapeutic intervention for chronic viral infections in the liver.