title: (-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus spontaneous lytic infection involves ERK1/2 and PI3-K/Akt signaling in EBV-positive cells.
abstract: Epstein-Barr virus (EBV) reactivation into the lytic cycle plays certain roles in the development of EBV-associated diseases, including nasopharyngeal carcinoma and lymphoma. In this study, we investigated the effects of the tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) on EBV spontaneous lytic infection and the mechanism(s) involved in EBV-positive cells. We found that EGCG could effectively inhibit the constitutive lytic infection of EBV at the DNA, gene transcription and protein levels by decreasing the phosphorylation and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt. By using cellular signaling pathway-specific inhibitors, we also explored the signaling mechanisms underlying the inhibitory effects of EGCG on EBV spontaneous lytic infection in cell models. Results show that specific inhibitors of Mitogen-Activated Protein Kinase Kinase (MEK) (PD98059) and phosphatidylinositol 3-kinase [PI3-K (LY294002)] markedly downregulated gene transcription and expression of BZLF1 and BMRF1 indicating that the MEK/ERK1/2 and PI3-K/Akt pathways are involved in the EBV spontaneous lytic cycle cascade. Therefore, one of the mechanisms by which EGCG inhibits EBV spontaneous lytic infection appears to involve the suppression of the activation of MEK/ERK1/2 and PI3-K/Akt signaling.
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Key Laboratory for Cancer and Invasion of Ministry of Education,  Changsha, Hunan 410078, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Liu
authors.forename: Hongde
authors.initials: H
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Lifang
authors.initials: L
authors.lastname: Yang
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Yongguan
authors.initials: Y
authors.lastname: Tao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Zijian
authors.initials: Z
authors.lastname: Li
authors.forename: Haidan
authors.initials: H
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004279:DNA, Viral / Q000378:metabolism; D004789:Enzyme Activation; D020031:Epstein-Barr Virus Infections / Q000378:metabolism / Q000821:virology; D005419:Flavonoids / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008223:Lymphoma / Q000378:metabolism / Q000821:virology; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000821:virology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014775:Virus Activation / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D002392:Catechin; D002867:Chromones; D004279:DNA, Viral; D005419:Flavonoids; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D014764:Viral Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C045651:epigallocatechin gallate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one