Effect of interferon alpha on hepatitis B virus replication and gene expression in transiently transfected human hepatoma cells.
OBJECTIVE
Chronic hepatitis B virus (HBV) infection is predominantly treated with interferon alpha (IFNalpha), which results in efficient reduction of the viral load only in 10-20% of treated patients. The mechanisms induced by IFNalpha resulting in reduction of viremia in responding patients are unknown. The aim of this study was to characterize HBV-specific IFNalpha-induced intracellular inhibitory mechanisms and IFNalpha-sensitive HBV targets.


METHODS
To determine the antiviral activity, cells transiently transfected with HBV DNA were treated with IFNalpha 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 IFNalpha-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 target region mediating IFNalpha-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 IFNa-induced antiviral mechanisms and HBV targets. At least two IFNalpha-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 IFNalpha-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.
Rang
A
A
Department of General Virology, Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany.
Günther
S
S
Will
H
H
D006528:Carcinoma, Hepatocellular; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects* / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007700:Kinetics; D008113:Liver Neoplasms; D012367:RNA, Viral / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D016898:Interferon-alpha; D012367:RNA, Viral