title: Cellular cIAP2 gene expression associated with anti-HBV activity of TNF-alpha in hepatoblastoma cells.
abstract: Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) can abolish HBV gene expression and replication through a noncytopathic mechanism mediated by tumor necrosis factor-alpha (TNF-alpha). However, the molecular mechanisms of TNF-alpha antiviral activity are not completely understood. To examine TNF-alpha-induced cellular responses and identify genes involved in anti-HBV activity, cDNA microarrays dotted with 14, 112 human genes were used to examine the transcriptional changes in HepG2 after treatment with TNF-alpha for 6 h. The results showed that many genes related to ligands and receptors, signal transduction including the TNF-alpha signaling pathway, mitochondrial and ribosomal proteins, and transcription regulation were induced by TNF-alpha. Interestingly, the TNF-alpha-inducible gene cIAP2 was found to inhibit HBV protein synthesis, viral replication, and transcription. Taken together, our results revealed the global effects of TNF-alpha treatment on hepatocellular gene expression. The antiviral genes identified by microarray could be developed as potential new anti-HBV drugs or for other novel therapies.
authors.affiliation: Key Laboratory of Medical Molecular Virology, Shanghai Medical College, and Institute of Biomedical Science and Microbiology, Fudan University, Shanghai 200032, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Liu
authors.forename: Junjie
authors.initials: J
authors.lastname: Shao
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Shiyan
authors.initials: S
authors.lastname: Yu
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Hu
authors.forename: Jiangxia
authors.initials: J
authors.lastname: Liu
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Xiang
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology; D006509:Hepatitis B / Q000188:drug therapy / Q000378:metabolism; D006515:Hepatitis B virus / Q000378:metabolism*; D018197:Hepatoblastoma / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D014409:Tumor Necrosis Factor-alpha