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
Fe. Zahm et al., 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, ITAL J GAST, 30(5), 1998, pp. 510-516
Citations number
31
Categorie Soggetti
Gastroenerology and Hepatology
Journal title
ITALIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
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.