Transcriptional profiling of Epstein-Barr virus (EBV) genes and host cellular genes in nasal NK/T-cell lymphoma and chronic active EBV infection

Br J Cancer. 2006 Feb 27;94(4):599-608. doi: 10.1038/sj.bjc.6602968.

Abstract

Nasal NK/T-cell lymphoma is an aggressive subtype of non-Hodgkin lymphoma (NHL) that is closely associated with Epstein-Barr virus (EBV). The clonal expansion of EBV-infected NK or T cells is also seen in patients with chronic active EBV (CAEBV) infection, suggesting that two diseases might share a partially similar mechanism by which EBV affects host cellular gene expression. To understand the pathogenesis of EBV-associated NK/T-cell lymphoproliferative disorders (LPD) and design new therapies, we employed a novel EBV DNA microarray to compare patterns of EBV expression in six cell lines established from EBV-associated NK/T-cell LPD. We found that expression of BZLF1, which encodes the immediate-early gene product Zta, was expressed in SNK/T cells and the expression levels were preferentially high in cell lines from CAEBV infection. We also analyzed the gene expression patterns of host cellular genes using a human oligonucleotide DNA microarray. We identified a subset of pathogenically and clinically relevant host cellular genes, including TNFRSF10D, CDK2, HSPCA, IL12A as a common molecular biological properties of EBV-associated NK/T-cell LPD and a subset of genes, such as PDCD4 as a putative contributor for disease progression. This study describes a novel approach from the aspects of viral and host gene expression, which could identify novel therapeutic targets in EBV-associated NK/T-cell LPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chronic Disease
  • Disease Progression
  • Epstein-Barr Virus Infections / complications*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Expression Regulation, Viral*
  • Herpesvirus 4, Human / genetics*
  • Herpesvirus 4, Human / pathogenicity*
  • Humans
  • Killer Cells, Natural
  • Lymphoma, T-Cell / pathology*
  • Lymphoma, T-Cell / virology*
  • Nose Neoplasms / pathology*
  • Nose Neoplasms / virology*
  • Oligonucleotide Array Sequence Analysis
  • Tumor Cells, Cultured