X-gene product antagonizes the p53-mediated inhibition of hepatitis B virus replication through regulation of the pregenomic/core promoter.

Employing the glutathione S-transferase column retention method and far Western analysis, we found a physical association between tumor suppressor p53 and the hepatitis B virus X-gene product, which led us to study the function of observed interaction in relation to viral propagation. In the cell culture-based in vitro replication system, expression of p53 resulted in dramatic inhibition of viral replication, and this inhibition was relieved by the coexpression of the X-gene product in a dose-dependent manner. Furthermore, the activity of pregenomic/core promoter, responsible for the synthesis of pregenomic RNA, was almost completely inhibited upon expression of p53, and as in the replication assay, the inhibition was rescued by the coexpression of the X-gene product in a dose-dependent manner. Based on these results, we propose that the ratio of X-gene product to p53 is an important factor determining the fate of viral replication through modulation of the pregenomic/core promoter.