Antiviral activity of ganciclovir, 9-(1,3-dihydroxy-2-propoxymethyl) guanine against woodchuck hepatitis virus: quantitative measurement of woodchuckhepatitis virus DNA using storage phosphor technology

Background & Aims. Ganciclovir is a nucleoside analogue active against cyto megalovirus. The compound has also shown in vitro and in vivo activity agai nst duck hepatitis B virus. We investigated the ability of ganciclovir to i nhibit another Hepadnaviridae, the woodchuck hepatitis virus, which is the most closely related with hepatitis B virus. We compared two different quan tification methods of woodchuck hepatitis virus DNA. Methods. We treated seven chronic woodchuck hepatitis virus carriers by dai ly intravenous injections of 5 mg/kg body weight of ganciclovir for seven c onsecutive days, and followed the animals for 3 weeks post therapy. In addi tion to traditional X-ray autoradiography, which is a semi-quantitative met hod, we evaluated woodchuck hepatitis virus DNA levels with storage phospho r technology. Results. A reduction in serum woodchuck hepatitis virus DNA was observed du ring treatment in all animals regardless of pre-treatment viraemia levels w hen using x-ray films and phosphor storage technology. The latter method al lowed calculation of mean values of average phosphor imager signals. When c omparing the mean values (+/- 95% confidence intervals) before and during t herapy a significant decrease in woodchuck hepatitis virus DNA (80 to 100%) could be shown. After stopping therapy, virus DNA rebounded in all animals . Conclusions. Our results show that ganciclovir inhibits viral replication i n woodchucks chronically infected with woodchuck hepatitis virus. No signs of toxicity were observed. After dot-blot hybridization, storage phosphor i maging was proven superior to X-ray autoradiography for measuring viral DNA . Storage phosphor technology is highly sensitive, quantitative and easy to handle. By comparing mean values and confidence intervals before and durin g therapy treatment effects can be distinguished from natural fluctuations.