title: NF-kappaB-mediated modulation of inducible nitric oxide synthase activity controls induction of the Epstein-Barr virus productive cycle by transforming growth factor beta 1.
abstract: Transforming growth factor beta 1 (TGF-β1) signal transduction has been implicated in many second-messenger pathways, including the NF-κB pathway. We provide evidence of a novel TGF-β1-mediated pathway that leads to extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, which in turn induces expression of an Epstein-Barr virus (EBV) protein, ZEBRA, that is responsible for the induction of the viral lytic cycle. This pathway includes two unexpected steps, both of which are required to control ERK 1/2 phosphorylation: first, a quick and transient activation of NF-κB, and second, downregulation of inducible nitric oxide synthase (iNOS) activity that requires the participation of NF-κB activity. Although necessary, NF-κB alone is not sufficient to produce downregulation of iNOS, suggesting that another uncharacterized event(s) is involved in this pathway. Dissection of the steps involved in the switch from the EBV latent cycle to the lytic cycle will be important to understand how virus-host relationships modulate the innate immune system.
authors.affiliation: UMR 1014 Inserm-Université Paris 11, Hôpital Paul Brousse, Bâtiment André Lwoff, 14 Avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France.
authors.forename: Lassad
authors.initials: L
authors.lastname: Oussaief
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ramírez
authors.forename: Aurélie
authors.initials: A
authors.lastname: Hippocrate
authors.forename: Hratch
authors.initials: H
authors.lastname: Arbach
authors.forename: Chantal
authors.initials: C
authors.lastname: Cochet
authors.forename: Alexis
authors.initials: A
authors.lastname: Proust
authors.forename: Martine
authors.initials: M
authors.lastname: Raphaël
authors.forename: Ridha
authors.initials: R
authors.lastname: Khelifa
authors.forename: Irène
authors.initials: I
authors.lastname: Joab
mesh_terms: D001402:B-Lymphocytes / Q000821:virology; D002460:Cell Line; D002461:Cell Line, Transformed; D015536:Down-Regulation; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014775:Virus Activation
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D016328:NF-kappa B; D015534:Trans-Activators; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3