title: The HBSP gene is expressed during HBV replication, and its coded BH3-containing spliced viral protein induces apoptosis in HepG2 cells.
abstract: The mechanisms of liver injury in hepatitis B virus (HBV) infection are defined to be due not to the direct cytopathic effects of viruses, but to the host immune response to viral proteins expressed by infected hepatocytes. We showed here that transfection of mammalian cells with a replicative HBV genome causes extensive cytopathic effects, leading to the death of infected cells. While either necrosis or apoptosis or both may contribute to the death of infected cells, results from flow cytometry suggest that apoptosis plays a major role in HBV-induced cell death. Data mining of the four HBV protein sequences reveals the presence of a Bcl-2 homology domain 3 (BH3) in HBSP, a spliced viral protein previously shown to be able to induce apoptosis and associated with HBV pathogenesis. HBSP is expressed at early stage of our cell-based HBV replication. When transfected into HepG2 cells, HBSP causes apoptosis in a caspase dependent manner. Taken together, our results suggested a direct involvement of HBV viral proteins in cellular apoptosis, which may contribute to liver pathogenesis.
authors.affiliation: School of Biological Sciences, College of Engineering, Nanyang Technological University, Singapore 637722, Singapore.
authors.forename: Yi Wei
authors.initials: YW
authors.lastname: Lu
authors.forename: Tuan Lin
authors.initials: TL
authors.lastname: Tan
authors.forename: Vincent
authors.initials: V
authors.lastname: Chan
authors.forename: Wei Ning
authors.initials: WN
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000502:physiology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004274:DNA, Recombinant / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D004274:DNA, Recombinant; C478361:HBSP protein, Hepatitis B virus; D014764:Viral Proteins