title: Inhibition of Epstein-Barr virus reactivation by the flavonoid apigenin.
abstract: BACKGROUND
  Lytic reactivation of EBV has been reported to play an important role in human diseases, including NPC carcinogenesis. Inhibition of EBV reactivation is considered to be of great benefit in the treatment of virus-associated diseases. For this purpose, we screened for inhibitory compounds and found that apigenin, a flavonoid, seemed to have the ability to inhibit EBV reactivation.
  
  
  METHODS
  We performed western blotting, immunofluorescence and luciferase analyses to determine whether apigenin has anti-EBV activity.
  
  
  RESULTS
  Apigenin inhibited expression of the EBV lytic proteins, Zta, Rta, EAD and DNase in epithelial and B cells. It also reduced the number of EBV-reactivating cells detectable by immunofluorescence analysis. In addition, apigenin has been found to reduce dramatically the production of EBV virions. Luciferase reporter analysis was performed to determine the mechanism by which apigenin inhibits EBV reactivation: apigenin suppressed the activity of the immediate-early (IE) gene Zta and Rta promoters, suggesting it can block initiation of the EBV lytic cycle.
  
  
  CONCLUSIONS
  Taken together, apigenin inhibits EBV reactivation by suppressing the promoter activities of two viral IE genes, suggesting apigenin is a potential dietary compound for prevention of EBV reactivation.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, No.35, Keyan Road, Zhunan Miaoli, Miaoli County, Taiwan. chungcwu@nhri.org.tw.
authors.forename: Chung-Chun
authors.initials: CC
authors.lastname: Wu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, No.35, Keyan Road, Zhunan Miaoli, Miaoli County, Taiwan.|Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, 116, Taiwan.
authors.forename: Chih-Yeu
authors.initials: CY
authors.lastname: Fang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, No.35, Keyan Road, Zhunan Miaoli, Miaoli County, Taiwan.
authors.forename: Yu-Jhen
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, No.35, Keyan Road, Zhunan Miaoli, Miaoli County, Taiwan.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Hsu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, No.35, Keyan Road, Zhunan Miaoli, Miaoli County, Taiwan.
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Chou
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, No.35, Keyan Road, Zhunan Miaoli, Miaoli County, Taiwan.
authors.forename: Sheng-Yen
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Department of Microbiology, College of Medicine National Health Research Institutes, National Taiwan University, No.35, Keyan Road, Zhunan Town, Miaoli County, Taipei, Taiwan.
authors.forename: Ching-Hwa
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, No.35, Keyan Road, Zhunan Miaoli, Miaoli County, Taiwan. cjy@nhri.org.tw.|Department of Microbiology, College of Medicine National Health Research Institutes, National Taiwan University, No.35, Keyan Road, Zhunan Town, Miaoli County, Taipei, Taiwan. cjy@nhri.org.tw.
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Chen
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D002460:Cell Line; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014775:Virus Activation / Q000187:drug effects*
chemical_list: D014764:Viral Proteins; D047310:Apigenin
keywords: Apigenin; Epstein-Barr virus; Nasopharyngeal carcinoma; Reactivation