The hepatitis B virus X protein transactivates viral core gene expression in vivo

The function of the X protein in the life cycle of mammalian hepadnaviruses is unclear. Based on tissue culture experiments it has been suggested that this protein represents a transcriptional transactivator which might be es sential for the expression of the viral core gene. Here we have examined wh ether the activity of the human hepatitis B virus (HBV) core gene in vivo d epends on X coexpression. To this end we compared core gene expression betw een four lineages of transgenic mice carrying the HBV core gene in cis arra ngement with the X gene (cex lineage) and six lineages containing a modifie d construct in which the start codon of the X gene had been deleted (ce lin eage). Whereas all cex lineages consistently exhibited a high-level hepatic core gene expression, the liver-specific core gene expression pattern of t he ce lineages was heterogenous,vith four lineages virtually not expressing the core gene. This defect was due to a strongly reduced transcription sin ce no core mRNA could be detected by Northern blotting. To test whether cor e gene expression could be restored by providing an intact;X gene in trans, we crossbred mice of two lines which expressed no core mRNA or core protei n with transgenic mice expressing the X-gene product under the transcriptio nal regulation of the liver-specific major-urinary-protein promoter/enhance r (MUP-X mice). The introduction of the MUP-X transgene induced core mRNA e xpression and core protein biosynthesis in the livers of the double-transge nic mice. This demonstrates that the X-gene product has the capacity to tra nsactivate HBV core gene expression in vivo.