INTERACTION OF INTERFERON-ALPHA WITH INTERLEUKIN-1-BETA OR TUMOR-NECROSIS-FACTOR-ALPHA ON HEPATITIS-B VIRUS ENHANCER ACTIVITY

The interaction of IFN-α with IL-1β or TNF-α on hepatitis B surface antigen (HBsAg) expression was analysed in hepatitis B virus (HBV)-DNA integrated PLC/PRF/5 and non-integrated HuH-7 human hepatoma cells. Secretion of HBsAg in PLC/PRF/5 cells was reduced by IFN-α, IL-1β or TNF-α, and synergistically depressed when -α was used in combination with IL-1β or TNF-α. By Northern blot analysis, the levels of HBsAg mRNA were suppressed by IFN-α in combination with IL-1β or TNF-α. In the chloramphenicol acetyltransferase plasmid transfection assay, IFN-α in combination with IL-1β or TNF-α caused a much greater suppression of HBV enhancer activity than IFN-α, IL-1β or TNF-α alone in both hepatoma cells. These findings suggest that the interaction of IFN-α with IL-1β or TNF-α synergistically represses HBV enhancer activity, resulting in depressed expression of HBsAg. © 1992.