Different activities of type I interferons on hepatitis B virus core promoter regulated transcription

The type I interferons (IFNs) are a group of closely related cytokines which have different signal transduction pathways and different biological activities. Using transient transfection of human hepatoma cells with reporter plasmids containing the firefly/renilla luciferase genes under the control of the HBV-Enhancer (Enh) I, Enh II and core promoter we have investigated the biological activities of 10 recombinant (r) type I IFNs on transcription. Low concentrations of IFN (0.025 ng/ml) had a significant and specific inhibitory effect but the potencies of the different recombinant type I IFNs differed markedly with IFNα8 and IFNβ being six-fold more potent than the least effective subtype (IFNα1). However, the addition of IFNα5 - the subtype produced predominantly in the human liver - did not cause any synergistic effects. The non-natural consensus IFN displayed a more pronounced inhibition of HBV-regulated transcription than IFNα8 or IFNα2 but not IFNβ. The INF-induced inhibitory effect was not dependent on the presence of the HBV-Enh1 and in particular of an interferon stimulated response element (ISRE)-like sequence. The characterization of different effects among type I interferons on HBV-regulatory elements may implicate an IFN-subtype-specific role for the pathogenesis and treatment of HBV-infection.