title: Luteolin inhibits Epstein-Barr virus lytic reactivation by repressing the promoter activities of immediate-early genes.
abstract: The lytic reactivation of Epstein-Barr virus (EBV) has been reported to be strongly associated with several human diseases, including nasopharyngeal carcinoma (NPC). Inhibition of the EBV lytic cycle has been shown to be of great benefit in the treatment of EBV-associated diseases. The administration of dietary compounds is safer and more convenient than other approaches to preventing EBV reactivation. We screened several dietary compounds for their ability to inhibit EBV reactivation in NPC cells. Among them, the flavonoid luteolin showed significant inhibition of EBV reactivation. Luteolin inhibited protein expression from EBV lytic genes in EBV-positive epithelial and B cell lines. It also reduced the numbers of EBV-reactivating cells detected by immunofluorescence analysis and reduced the production of virion. Furthermore, luteolin reduced the activities of the promoters of the immediate-early genes Zta (Zp) and Rta (Rp) and also inhibited Sp1-luc activity, suggesting that disruption of Sp1 binding is involved in the inhibitory mechanism. CHIP analysis revealed that luteolin suppressed the activities of Zp and Rp by deregulating Sp1 binding. Taken together, luteolin inhibits EBV reactivation by repressing the promoter activities of Zp and Rp, suggesting luteolin is a potential dietary compound for prevention of virus infection.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chung-Chun
authors.initials: CC
authors.lastname: Wu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, 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, Zhunan, Taiwan.
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Hsu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yen-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Chou
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Sheng-Yen
authors.initials: SY
authors.lastname: Huang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yu-Jhen
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Lin
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ching-Hwa
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan; Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: cjy@nhri.org.tw.
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D020031:Epstein-Barr Virus Infections / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D017781:Genes, Immediate-Early; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014775:Virus Activation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D047311:Luteolin
keywords: Epstein-Barr virus; Flavonoid; Luteolin; Lytic cycle; Nasopharyngeal carcinoma; Sp1