X-GENE PRODUCT ANTAGONIZES THE P53-MEDIATED INHIBITION OF HEPATITIS-BVIRUS-REPLICATION THROUGH REGULATION OF THE PREGENOMIC CORE PROMOTER/

Employing the glutathione S-transferase column retention method and fa r Western analysis, we found a physical association between tumor supp ressor p53 and the hepatitis B virus X-gene product, which led us to s tudy the function of observed interaction in relation to viral propaga tion, In the cell culture-based in vitro replication system, expressio n of p53 resulted in dramatic inhibition of viral replication, and thi s 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 replicatio n 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 determ ining the fate of viral replication through modulation of the pregenom ic/core promoter.