Epstein-Barr virus nuclear antigen 2 induces interleukin-18 receptor expression in B cells.
Epstein-Barr virus (EBV) latently infects and immortalizes B lymphocytes and causes lymphoproliferative malignancies. We show here that the EBV nuclear antigen EBNA2 induces expression of the 2 chains of the interleukin-18 receptor (IL-18R) in Burkitt lymphoma (BL) cell lines and in nontransformed B cells. Activation of IL-18R expression by EBNA2 is independent of its interaction with the transcriptional repressor RBPJ kappa. It occurs in the absence of any other viral protein but requires de novo synthesis of cellular proteins. IL-18R induction is a highly specific function of EBNA2, because neither other EBV latent proteins nor the cellular proteins c-myc or Notch can exert this effect. Using cDNA microarray expression profiling, we find that the IL-18 receptor expressed in EBV-infected BL cells has signaling capacity, because IL-18 significantly modified gene expression. We report that EBNA2 expression is associated with IL-18R expression in vivo in EBV-positive B-lymphomas from AIDS patients.
Pagès
Franck
F
Institut National de la Santé et de la Recherche Médicale (INSERM) U255, Centre de Recherche Biomédicale des Cordeliers, Paris, France.
Galon
Jérôme
J
Karaschuk
Galina
G
Dudziak
Diana
D
Camus
Mathieu
M
Lazar
Vladimir
V
Camilleri-Broët
Sophie
S
Lagorce-Pagès
Christine
C
Lebel-Binay
Sophie
S
Laux
Gerhard
G
Fridman
Wolf-Herman
WH
Henglein
Berthold
B
D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D002051:Burkitt Lymphoma / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis / Q000502:physiology*; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D053727:Interleukin-18 Receptor alpha Subunit; D016483:Lymphoma, AIDS-Related / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000378:metabolism / Q000821:virology; D021122:Protein Subunits / Q000096:biosynthesis / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D053724:Receptors, Interleukin-18; D014764:Viral Proteins; D015678:Viral Structural Proteins / Q000235:genetics
C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; C508572:IL18R1 protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D021122:Protein Subunits; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D014764:Viral Proteins; D015678:Viral Structural Proteins