title: Inhibition of the Epstein-Barr virus lytic cycle by protoapigenone.
abstract: Epstein-Barr virus (EBV) expresses two transcription factors, Rta and Zta, during the immediate-early stage of the lytic cycle to activate the transcription of early and late genes. This study finds that 0.31 mM protoapigenone from Thelypteris torresiana (Gaud.) inhibits the expression of EBV lytic proteins, including Rta, Zta, EA-D and VCA, in P3HR1 cells after lytic induction with 12-O-tetradecanoylphorbol-13-acetate and sodium butyrate. The lack of expression of EBV lytic proteins after protoapigenone treatment is attributed to the inhibition of the transactivation function of Zta because protoapigenone reduces the transactivation activity of Zta and Gal4-Zta, which contains the transactivation domain of Zta fused with Gal4. In contrast, protoapigenone does not affect the ability of Rta to activate a promoter that contains an Rta-response element, showing that the inhibition is unrelated to Rta. Furthermore, in a lactate dehydrogenase assay, protoapigenone is not toxic to P3HR1 cells at the concentrations that inhibit the function of Zta, showing that protoapigenone is valuable for studying the function of Zta and preventing EBV lytic proliferation.
authors.affiliation: Department of Microbiology and Immunology, Chang-Gung University, Kwei-Shan 333, Taiwan, ROC.
authors.forename: Chao-Ping
authors.initials: CP
authors.lastname: Tung
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
authors.affiliation: Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan, ROC.
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan, ROC.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Chuang
authors.affiliation: Institute of Pharmacognosy, University of Szeged, Eotvos str. 6, H-6720 Szeged, Hungary.|Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan, ROC.
authors.forename: Attila
authors.initials: A
authors.lastname: Hunyadi
authors.affiliation: Department of Microbiology and Immunology, Chang-Gung University, Kwei-Shan 333, Taiwan, ROC.
authors.forename: Shih-Tung
authors.initials: ST
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D003512:Cyclohexanones / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000821:virology; D029624:Ferns / Q000737:chemistry*; D047309:Flavones / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D003512:Cyclohexanones; D047309:Flavones; D010936:Plant Extracts; D014764:Viral Proteins; C524112:protoapigenone