Latent Membrane Protein 1 of Epstein-Barr Virus Induces CD83 by the NF-κB Signaling Pathway

• DOI: 10.1128/jvi.77.15.8290-8298.2003
• Publication Date: 2003-07-12T13:13:13Z
• Authors: Diana Dudziak; Arnd Kieser; Ulrike Dirmeier; Falk Nimmerjahn; Susanne Berchtold; Alexander Steinka...; Gabriele Marschall; Wolfgang Hammersc...; Gerhard Laux; Georg W. Bornkamm
• Keywords: 0301 basic medicine; B-Lymphocytes; Herpesvirus 4, Human; Membrane Glycoproteins; NF-kappa B; Immunoglobulins; Estrogens; Receptors, Tumor Necrosis Factor; Up-Regulation; 3. Good health; Viral Matrix Proteins; Viral Proteins; 03 medical and health sciences; Epstein-Barr Virus Nuclear Antigens; Antigens, CD; CD83 Antigen; Humans; CD40 Antigens; Promoter Regions, Genetic; Gene Deletion; Cell Line, Transformed; Signal Transduction

ABSTRACT Epstein-Barr virus (EBV) infects human resting B cells and transforms them in vitro into continuously growing lymphoblastoid cell lines (LCLs). EBV nuclear antigen 2 (EBNA2) is one of the first viral proteins expressed after infection. It able to transactivate as well cellular target genes by interaction with transcription factors. EBNA2 can be studied easily using an LCL (ER/EB2-5) which wild-type replaced estrogen-inducible EBNA2. Since surface molecule CD83, a member immunoglobulin superfamily marker for mature dendritic cells, appeared on ER/EB2-5 within 3 h addition estrogen, we analyzed regulation CD83 induction more detail. Despite its rapid induction, turned out indirect gene We could show that latent membrane protein 1 (LMP1) responsible expressing ligand- or antibody-inducible recombinant nerve growth factor receptor-LMP1 fusion protein. The inducibility promoter LMP1 was mediated activation NF-κB, seen use luciferase reporter assays mutants. Additionally, constructs transmembrane domain intracellular signaling CD40, TNF-R1, TNF-R2 likewise transactivated via NF-κB. Our studies also NF-κB pathway cells.