CELL-TYPE-SPECIFIC MECHANISMS REGULATE HEPATITIS-B VIRUS TRANSGENE EXPRESSION IN LIVER AND OTHER ORGANS

Intracellular expression of hepatitis B virus (HBV) was analysed in tr ansgenic HBV mouse lines designated G7 and G26, the former lacking hep atitis B surface antigen (HBsAg) promoters. HBsAg mRNA expression was greater in the G26 line than in the G7 line, although in situ hybridiz ation showed a qualitatively similar expression pattern in specific ce ll types. HBsAg mRNA was most abundant in hepatocytes, followed in mag nitude by proximal renal tubular epithelial cells, pancreatic acinar c ells, and epithelial cells of the gastric, small intestinal, and bronc hiolar mucosae. In biliary epithelial cells, brain, spleen, large inte stine, testis, heart, and skeletal muscle, HBsAg mRNA was undetectable . In cell transfection assays, the HBV enhancer/preS1 promoter efficie ntly expressed a luciferase reporter with appropriate upregulation by HNF-3 alpha and C/EBP alpha transcription factors in hepatocyte-derive d cells but not in non-parenchymal epithelial liver cells or fibroblas ts. These results suggest that cell-type specificity of HBV expression is regulated by interactions between viral elements and cellular tran sactivators. Variable expression of G7 and G26 HBV transgenes in epith elial cells combined with differences in transgene expression in simil ar sets of cells suggests at least two levels of regulation: one direc ting cell specificity of HBV expression and the other governing quanti tative expression of HBV mRNA.