Demonstration of duck hepatitis B virus in bile duct epithelial cells: Implications for pathogenesis and persistent infection

Abstract

ogy, genomic organization, and replication by means of reHepatitis B virus (HBV) has been demonstrated in bile verse transcription. 1,3 duct epithelial cells (BDEC) during chronic infection.The replication of human HBV has been extensively studThe persistence of virus in BDEC may play an important ied in hepatocytes, but comparatively less is known about role in disease pathogenesis, and may be at least partly HBV infection of nonparenchymal cells within the liver. Hepresponsible for the relapse phenomenon observed in adnaviral antigens have been shown in bile duct epithelial antiviral treatments using nucleoside analogues. The cells (BDEC) in both human 7,8 and animal 9,10 livers, but the aims of this study were to examine the morphological significance of these findings has not been fully determined. changes within the liver in the duck hepatitis B modelThe HBV life cycle is complex, and there is evidence that following bile duct ligation (BDL), and to assess the efit may vary depending on the cell type, such as lymphoid fect of biliary hyperplasia upon viral DNA and proteins.cells compared with hepatocytes. 11-15 Also, HBV replication Seven-day-old ducklings, congenitally infected with the appears to be cell-cycle dependent with enhanced viral repliduck hepatitis B virus (DHBV), were subject to BDL. The cation occurring in quiescent compared with proliferating hepathological and virological changes were then followed patocytes. 16 Recent studies have shown that HBV replication at 5, 10, 15, and 20 days after ligation. All results were is inversely correlated with cellular DNA synthesis with noncompared with age-matched unligated control birds cytolytic cell arrest resulting in increased viral expression. 16 congenitally infected with DHBV. To assess the earlyIn contrast, stimulation of viral replication with release of morphological changes, additional animals were sacrimature woodchuck HBV has been shown in viral-infected ficed at 1, 2, 3, and 4 days post-BDL. The proportion of mitogen stimulated B-lymphocytes, but not resting cells. 12 DHBV-infected BDEC, was examined by immunohisto-BDEC comprise only 2% to 5% of cells in the liver, yet chemistry and in situ hybridization. BDL induced rapid represent a potentially important reservoir of HBV infection biliary hyperplasia, with a doubling time for BDEC of that is relatively resistant to eradication by antiviral agents. 9 1.3 days. The proliferated BDEC displayed immunohistoTherefore, the interaction of HBV with BDEC warrants more chemical features identical to resting BDEC. More than detailed investigation. The aim of the present study was to 50% of BDEC in unligated controls, and more than 46% characterize DHBV infection in BDEC of congenitally inof proliferated BDEC in ligated animals were positive fected animals, and to examine the effect of cell division on for DHBV DNA and structural proteins. The intensity of hepadnaviral proteins and DNA in proliferating BDEC using immunohistochemical staining and in situ hybridization immunohistochemistry and in situ ...