title: Epstein-Barr virus infection leads to partial phenotypic reversion of terminally differentiated malignant B cells.
abstract: The B cell lymphomas associated with Epstein-Barr virus (EBV) are not limited to any specific stage of B cell differentiation but covers widely different B cell phenotypes. In vitro infection of the virus negative tumors with a recombinant EBV strain has provided important insights into virus-tumor interaction. Here, we investigated the interaction between EBV and terminally differentiated tumor derived B cells, namely multiple myeloma (MM). The in vitro EBV infected MM expressed restricted viral latency. Acquisition of the virus was accompanied by a partial reprogramming to a mature B cell phenotype. Thus, the plasma cell markers syndecan-1 (CD138), Blimp1 and MUM1 were downregulated, while expression of HLADR, CIITA and TCL1, which are normally not expressed in plasmacytoid cells, was upregulated. The silenced transcription factor gene encoding Pax5 and its target BLNK were activated. Significantly, the free lambda light chains secreted in the medium were reduced in EBV infected MM clones. Collectively, these results suggest that the restricted EBV latency can cause at least partial phenotypic reversion of terminally differentiated B tumor cells. We suggest that the restricted EBV latent gene expression may not only be the consequence but the cause of the mature B cell phenotype, actively participating in the virus persistence.
authors.affiliation: Istituto Pasteur-Fondazione Cenci-Bolognetti, Department of Experimental Medicine and Pathology, University of Rome La Sapienza Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Eleni
authors.initials: E
authors.lastname: Anastasiadou
authors.forename: Signe
authors.initials: S
authors.lastname: Vaeth
authors.forename: Laura
authors.initials: L
authors.lastname: Cuomo
authors.forename: Francesco
authors.initials: F
authors.lastname: Boccellato
authors.forename: Sara
authors.initials: S
authors.lastname: Vincenti
authors.forename: Mara
authors.initials: M
authors.lastname: Cirone
authors.forename: Carlo
authors.initials: C
authors.lastname: Presutti
authors.forename: Steffen
authors.initials: S
authors.lastname: Junker
authors.forename: Gösta
authors.initials: G
authors.lastname: Winberg
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
authors.forename: Paul A
authors.initials: PA
authors.lastname: Wade
authors.forename: Alberto
authors.initials: A
authors.lastname: Faggioni
authors.forename: Pankaj
authors.initials: P
authors.lastname: Trivedi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000235:genetics; D050835:Interferon Regulatory Factors / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D009101:Multiple Myeloma / Q000473:pathology*; D009194:Myeloma Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D051757:PAX5 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D010641:Phenotype; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D053668:Syndecan-1 / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000473:pathology / Q000821:virology; D017735:Virus Latency; D000099218:Interferon Regulatory Factor-4
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007146:Immunoglobulin lambda-Chains; D050835:Interferon Regulatory Factors; D035683:MicroRNAs; D009194:Myeloma Proteins; D009363:Neoplasm Proteins; D051757:PAX5 Transcription Factor; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D053668:Syndecan-1; D000099218:Interferon Regulatory Factor-4; C113939:B cell linker protein; C532045:MIRN29a microRNA, human; C497281:PAX5 protein, human; C508241:SDC1 protein, human; C090851:TCL1A protein, human; C087042:PRDM1 protein, human