title: Down-regulation of spontaneous Epstein-Barr virus reactivation in the P3HR-1 cell line by L-arginine.
abstract: We tested the hypothesis that inhibition of Epstein-Barr virus (EBV) reactivation is controlled in part by nitric oxide (NO) generated from L-arginine (Arg). The spontaneous reactivation of EBV in the Burkitt's lymphoma (BL) cell line P3HR-1 was inhibited when the cells were cultured in L-Arg-supplemented medium. The expression of EBV early antigen (EA), immediate-early BZLF1 mRNA and the protein ZEBRA, and production of infectious virus were reduced by L-Arg supplementation in a dose-dependent manner. We demonstrated that inducible NO synthase (iNOS) mRNA was constitutively expressed in P3HR-1 cells, as quantitated by the reverse transcription-polymerase chain reaction. L-Arg supplementation enhanced iNOS and NOx expression in the cells. A specific NOS inhibitor, NG-monomethyl-L-Arg enhanced the expression of ZEBRA and early BMRF1 protein EA-D in the cells. L-Arg supplementation also inhibited the spontaneous EBV reactivation in another BL cell line EB1 and a B lymphoblastoid cell line OB. These results indicated that L-Arg induces iNOS and generates NO, which inhibits EBV reactivation in EBV-positive cells.
authors.affiliation: Department of Biosignaling, School of Life Science, Faculty of Medicine, Tottori University, Yonago, 683-8503, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Agawa
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Ikuta
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Minamiyama
authors.forename: Masayasu
authors.initials: M
authors.lastname: Inoue
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sairenji
mesh_terms: D001120:Arginine / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D015534:Trans-Activators / Q000096:biosynthesis; D014764:Viral Proteins; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II