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

Eleni Anastasiadou, Signe Vaeth, Laura Cuomo, Francesco Boccellato, Sara Vincenti, Mara Cirone, Carlo Presutti, Steffen Junker, Gösta Winberg, Luigi Frati, Paul A. Wade, Alberto Faggioni, Pankaj Trivedi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)165-174
Number of pages10
JournalCancer Letters
Volume284
Issue number2
DOIs
Publication statusPublished - Nov 1 2009

Keywords

  • Differentiation
  • EBV
  • Latency
  • Myeloma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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