TY - JOUR

T1 - Epstein-Barr virus infection leads to partial phenotypic reversion of terminally differentiated malignant B cells

AU - Anastasiadou, Eleni

AU - Væth, Signe

AU - Cuomo, Laura

AU - Boccellato, Francesco

AU - Vincenti, Sara

AU - Cirone, Mara

AU - Presutti, Carlo

AU - Junker, Steffen

AU - Winberg, Gösta

AU - Frati, Luigi

AU - Wade, Paul A

AU - Faggioni, Alberto

AU - Trivedi, Pankaj

N1 - 2009 Elsevier Ireland Ltd.

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Adaptor Proteins, Signal Transducing

KW - B-Cell-Specific Activator Protein

KW - B-Lymphocytes

KW - Cell Differentiation

KW - Gene Expression Regulation, Neoplastic

KW - Gene Expression Regulation, Viral

KW - Genes, Viral

KW - Herpesvirus 4, Human

KW - Humans

KW - Immunoglobulin lambda-Chains

KW - Interferon Regulatory Factors

KW - MicroRNAs

KW - Multiple Myeloma

KW - Myeloma Proteins

KW - Neoplasm Proteins

KW - Phenotype

KW - Proto-Oncogene Proteins

KW - Repressor Proteins

KW - Syndecan-1

KW - Tumor Cells, Cultured

KW - Virus Latency

U2 - 10.1016/j.canlet.2009.04.025

DO - 10.1016/j.canlet.2009.04.025

M3 - Journal article

C2 - 19481340

VL - 284

SP - 165

EP - 174

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 2

ER -