penciclovir and Hepatoblastoma

The HBV-producing human hepatoblastoma cell line, 2.2.15, has been shown to be an accurate model of chronic cellular viral infection and a predictive model of antiviral response for in vivo hepadnaviral infection. Our laboratory has utilized the 2.2.15 cell line in a standardized assay to examine treatment schemes which use combinations of clinically relevant nucleoside analogues, novel methods to deliver potentially useful nucleoside combinations, and treatments which simultaneously target different parts of the HBV replication pathway. For example, the combination of 3TC (lamivudine) with either alpha interferon or penciclovir significantly enhances the antiviral effectiveness of these agents against HBV replication in 2.2.15 cell culture.

Topics: Acyclovir; Antiviral Agents; Drug Synergism; Drug Therapy, Combination; Guanine; Hepatitis B; Hepatitis B virus; Hepatoblastoma; Humans; Interferon-alpha; Lamivudine; Tumor Cells, Cultured; Virus Replication; Zalcitabine

Penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yI)guanine], an effective antiherpesvirus agent, was found to be a potent and selective antiviral agent against intracellular hepatitis B virus (HBV) replication (drug concentration at which a 10-fold decrease in HBV DNA from the average level in an untreated culture was observed [EC90], 1.6 microM) and extracellular virion release (EC90, 0.7 microM) by cultured human hepatoblastoma (2.2.15) cells. Acyclovir and three other related 9-alkoxypurines with activity against either herpesviruses or human immunodeficiency virus were uniformly inactive against HBV. The activity of penciclovir is discussed in relation to recent findings related to its mode of action against HBV.

Topics: Acyclovir; Antiviral Agents; Cell Line; Dideoxynucleosides; DNA-Directed DNA Polymerase; Guanine; Hepatitis B virus; Hepatoblastoma; Humans; Lamivudine; Microbial Sensitivity Tests; Virus Replication