Effect of interferon alpha on hepatitis B virus replication and gene expression in transiently transfected human hepatoma cells

Background/Aims: Chronic hepatitis B virus (HBV) infection is predominantly treated with interferon alpha (IFN alpha), which results in efficient reduction of the viral load only in 10-20% of treated patients. The mechanisms induced by IFN alpha resulting in reduction of viremia in responding patients are unknown. The aim of this study was to characterize HBV-specific IFN alpha-induced intracellular inhibitory mechanisms and IFN alpha-sensitive HBV targets. Methods: To determine the antiviral activity, cells transiently transfected with HBV DNA were treated with IFNa and thereafter, viral products were quantified at different time points, Results: Time-dependent reduction of RNA, replicative DNA-intermediates, core protein and secreted HBsAg/HBeAg levels was observed in IFN alpha-treated cells. Viral RNA levels were reduced most effectively early post-treatment whereas those of core protein and replicative intermediates decreased later. By expression of subgenomic HBV sequences, an RNA tar-get region mediating IFN alpha-induced RNA degradation was mapped. Conclusions: These data indicate that HuH7 cells transiently transfected with HBV-DNA represent a system well suited for detailed analysis of IFN alpha-induced antiviral mechanisms and HBV targets. At least two IFN alpha-induced HBV-specific antiviral activities are active in this system: one reduces the levels of core protein and replicative intermediates, the other leads to posttranscriptional degradation of HBV-RNA. Based on the established in vitro system a detailed characterization of the IFN alpha-sensitive RNA-region and of factors mediating this intracellular antiviral effect is feasible, This may lead to the development of novel strategies for therapy of chronic hepatitis.