The aim of this study is to characterize the role of
ellagic acid, a
flavonoid from a medicinal herb which blocks
HBeAg secretion in a HBV infected cell line and in
HBeAg transgenic mice, in immune tolerance in chronic HBV
infection. Using the mouse strain C57ML/6,
HBeAg-producing transgenic mice (
HBeAg-Tg), under the control of
metal ion-inducible promoter were generated. The effect on immune tolerance of
HBeAg-Tg and the release of immune tolerance by the inhibitor of
HBeAg secretion,
ellagic acid, was tested using T/B cell proliferation,
HBeAg/HBeAb production, cytotoxic T-lymphocyte (CTL) and
cytokine assays. C57ML/6 based
HBeAg-producing
HBeAg-Tg mice were tolerant to
HBeAg at the T and B-cell level, did not produce
antibodies to
HBeAg in vivo and in vitro, produced minimal levels of
cytokines (IL-4 and IFN-gamma) and decreased CTL responses, while feeding mice with
ellagic acid (5mg/kg
body weight) blocked the immune tolerance caused by
HBeAg. Our results suggest that host immune tolerance induced by
HBeAg during HBV
infection, a viral strategy to guarantee HBV
infection, can be overcome by
ellagic acid, thus it can be used as a therapeutic for HBV-carriers.