title: Specific expression of human interferon-gamma controls hepatitis B virus replication in vitro in secreting hepatitis B surface antigen hepatocytes.
abstract: Interferon-gamma (IFN-γ) has been reported to have antiviral activity against Hepatitis B virus (HBV) and to suppress HBV replication noncytolytically in vivo. Since systemic administration of IFN-γ may cause severe adverse effects, studies of the effects of liver-specific IFN-γ expression from adenoviral vectors in vivo have been investigated. In this study, a novel strategy has been described that drives specific expression of human IFN-γ in HBsAg-secreting hepatocytes. A bicistronic expression vector has been developed, pcDNA3.1-HBV antisense S gene-HCV core protein gene-HCV internal ribosome entry sites (IRES)-IFN-γ (pcDNA-SCIγ), by inserting four DNA fragments into pcDNA3.1. Tight modulation of HCV IRES-dependent translation by the HCV core protein was achieved using an antisense RNA technique with a bicistronic expression vector. HepG2 cells and HepG2.2.15 cells stably expressing HBV were transduced with pcDNA-SCIγ to test the responsiveness of IFN-γ to HBsAg expression. Gene transfer resulted in a low background and a 30-fold induction of IFN-γ expression from pcDNA-SCIγ in a cell-specific fashion. Hepatocyte-specific IFN-γ expression controlled effectively HBV replication in HBsAg-secreting HepG2.2.15 cells without cell toxicity.
authors.affiliation: The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China. Kanqc@yahoo.com.cn
authors.forename: Quancheng
authors.initials: Q
authors.lastname: Kan
authors.forename: Duolu
authors.initials: D
authors.lastname: Li
authors.forename: Zujiang
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology*; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D007371:Interferon-gamma