ALTERATIONS IN INTRAHEPATIC EXPRESSION OF DUCK HEPATITIS-B VIRAL MARKERS WITH GANCICLOVIR CHEMOTHERAPY

Ducks congenitally infected with duck hepatitis B virus (DHBV) were tr eated with the guanosine analogue, ganciclovir, and the effect on seru m and intrahepatic expression of DHBV DNA and viral proteins was exami ned. After 21 days of ganciclovir treatment, a substantial reduction i n viraemia occurred; in contrast, the level of circulating DHBV surfac e antigen was unchanged. Ganciclovir therapy also substantially reduce d the level of DHBV DNA replicative intermediates and the expression o f viral core and surface antigen in hepatocytes. However, despite the antiviral treatment some liver cells, including the bile duct epitheli al cells and putative oval cells, maintained their intense staining fo r the viral proteins. Furthermore, DHBV-infected cells in extrahepatic sites such as the pancreas, kidney and spleen were also unaffected by ganciclovir treatment. These results suggest that monotherapy with nu cleoside analogues is unlikely to eliminate chronic hepadnaviral infec tion, and antiviral programs should be designed to target all cell pop ulations infected by the virus.