title: Lytic Epstein-Barr virus infection in epithelial cells but not in B-lymphocytes is dependent on Blimp1.
abstract: Epstein-Barr virus (EBV) replicates in superficial differentiated cells of oral hairy leukoplakia (OHL). Differentiation of squamous epithelial cells depends on B-lymphocyte-induced maturation protein 1 (Blimp1). Here we show that expression of the EBV immediate-early protein BZLF1 is restricted to Blimp1-positive epithelial cells in OHL. Luciferase assays revealed Blimp1-dependent induction of the BZLF1 promoter Zp in epithelial cell lines. Expression of ZEB1, a negative regulator of Zp, and of Xbp-1, which mediates the Blimp1 effect on Zp in B-cells, was not affected by enforced Blimp1 expression. Moreover, Xbp-1 protein expression was not detected in differentiated epithelial cells of OHL. Thus, Blimp1 induces BZLF1 expression in epithelial cells independently of ZEB1 and Xbp-1. In contrast to epithelial cells of OHL, BZLF1 expression was also observed in Blimp1-negative lymphoid cells in infectious mononucleosis tonsils, suggesting that EBV replication in B-cells may be induced independently of terminal differentiation.
authors.affiliation: Institute for Pathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Buettner
authors.affiliation: Division of Molecular Immunology, Nikolaus Fiebiger Center, Department of Internal Medicine III, University Hospital Erlangen, Erlangen, Germany.|Institute for Pathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Lang
authors.affiliation: Institute for Pathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Christiane S
authors.initials: CS
authors.lastname: Tudor
authors.affiliation: Institute for Pathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Meyer
authors.affiliation: Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Cruchley
authors.affiliation: Institute for Pathology, Sana Klinikum Lichtenberg/Unfallkrankenhaus Berlin, Berlin, Germany.
authors.forename: Mario Henrique M
authors.initials: MHM
authors.lastname: Barros
authors.affiliation: Department of Virology, Imperial College Faculty of Medicine, St Mary's Campus, London, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Farrell
authors.affiliation: Division of Molecular Immunology, Nikolaus Fiebiger Center, Department of Internal Medicine III, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Jäck
authors.affiliation: Division of Molecular Immunology, Nikolaus Fiebiger Center, Department of Internal Medicine III, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schuh
authors.affiliation: Institute for Pathology, Sana Klinikum Lichtenberg/Unfallkrankenhaus Berlin, Berlin, Germany.|Institute for Pathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Niedobitek
mesh_terms: D001402:B-Lymphocytes / Q000821:virology*; D004847:Epithelial Cells / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000254:growth & development / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D012097:Repressor Proteins; D015534:Trans-Activators; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1