EBV latency III immortalization program sensitizes B cells to induction of CD95-mediated apoptosis via LMP1: role of NF- B, STAT1, and p53
| Autor: | Georg W. Bornkamm, Jean Feuillard, Ibtissam Youlyouz-Marfak, Christophe Le Clorennec, Eric Adriaenssens, Jean Coll |
|---|---|
| Přispěvatelé: | Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Université de Limoges (UNILIM) |
| Rok vydání: | 2006 |
| Předmět: |
MESH: Signal Transduction
Epstein-Barr Virus Infections Herpesvirus 4 Human MESH: I-kappa B Proteins T-Lymphocytes MESH: Membrane Glycoproteins MESH: NF-kappa B Apoptosis MESH: Estrogens Biochemistry chemistry.chemical_compound NF-KappaB Inhibitor alpha MESH: Genetic Vectors hemic and lymphatic diseases MESH: Animals MESH: Interferon-Stimulated Gene Factor 3 STAT1 MESH: Tumor Suppressor Protein p53 Genes Dominant B-Lymphocytes Membrane Glycoproteins MESH: Epstein-Barr Virus Infections biology NF-kappa B [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology hemic and immune systems MESH: Tumor Necrosis Factors Interferon-Stimulated Gene Factor 3 Hematology Transfection Fas receptor MESH: Gene Expression Regulation MESH: Antigens CD95 Cell biology MESH: Cell Transformation Viral Tumor Necrosis Factors I-kappa B Proteins MESH: Epstein-Barr Virus Nuclear Antigens Plasmids Signal Transduction MESH: Mutation MESH: Cell Line Tumor Fas Ligand Protein Genetic Vectors Immunology Virus Viral Matrix Proteins Viral Proteins Immune system MESH: Plasmids MESH: B-Lymphocytes Cell Line Tumor otorhinolaryngologic diseases Animals Humans fas Receptor MESH: Viral Matrix Proteins MESH: Humans MESH: Apoptosis MESH: Herpesvirus 4 Human Estrogens NF-κB Cell Biology Cell Transformation Viral MESH: Viral Proteins MESH: Fas Ligand Protein IκBα MESH: T-Lymphocytes Epstein-Barr Virus Nuclear Antigens Gene Expression Regulation chemistry Mutation biology.protein Cancer research Tumor Suppressor Protein p53 MESH: Genes Dominant |
| Zdroj: | Blood Blood, American Society of Hematology, 2006, 107 (5), pp.2070-8. ⟨10.1182/blood-2005-05-2053⟩ |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Epstein-Barr virus (EBV) induces CD95 expression and the CD95 gene (FAS) is regulated by NF-kappaB, STAT1, and/or p53. To understand the contribution of these factors in the regulation of CD95 by EBV in lymphoblastoid cell lines (LCLs), we cloned dominant-active IkappaBalpha, active (STAT1alpha) and inactive (STAT1beta) forms of STAT1, p53, a dominant-negative mutant of LMP1, and wild-type LMP1 into a novel double-inducible episomal vector, pRT-1. These plasmids were stably transfected either into wild-type LCLs or EREB2-5 cells, an LCL with an estrogen-regulatable EBNA2 protein. Inhibition of LMP1 signaling decreased expression of CD95, whereas overexpression of LMP1 markedly increased it. Induction of the latency III program in EREB2-5 cells correlated with activation of NF-kappaB, STAT1, and p53. CD95 expression was regulated by these 3 transcriptional systems. STAT1 and p53 activation were secondary to NF-kappaB activation. CD95 surface expression sensitized EBV-infected B cells to the induction of CD95-mediated apoptosis. In vitro inhibition of CD95-CD95 ligand interaction was found to reverse T-cell killing of EBV-infected B cells. Therefore, LMP1 activation of NF-kappaB sensitizes infected B cells to CD95-mediated apoptosis and renders EBV latency III-immortalized B cells susceptible to elimination by the immune system, contributing to the establishment of a host/virus equilibrium. |
| Databáze: | OpenAIRE |
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