FIG 8.

Model for the role of β-catenin in regulating HBV biosynthesis in HBV transgenic mice. HBV replication occurs within the assembling capsids in the cytoplasm of hepatocytes. Thus, cytoplasmic staining of HBcAg serves as a readout of the lobular distribution of viral replication (14). β-Catenin activity directs robust HBV transcription immediately proximal to the central vein via endothelial cell-derived Wnt signaling (15). This poorly diffusible signal rapidly diminishes across the liver lobule (15). Lower levels of viral replication present in midzone and periportal zone 1 hepatocytes appear to be supported by viral transcription that is independent of direct β-catenin activity. In the absence of β-catenin activity, robust HBV biosynthesis is lost from pericentral zone 3 hepatocytes with compensating viral transcription and hence enhanced capsid biosynthesis expanding to include periportal zone 1 hepatocytes.