Transcriptional profiling of Epstein-Barr virus (EBV) genes and host cellular genes in nasal NK/T-cell lymphoma and chronic active EBV infection.
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.
Zhang
Y
Y
First Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan.
Ohyashiki
J H
JH
Takaku
T
T
Shimizu
N
N
Ohyashiki
K
K
D002908:Chronic Disease; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D007694:Killer Cells, Natural; D016399:Lymphoma, T-Cell / Q000473:pathology* / Q000821:virology*; D009669:Nose Neoplasms / Q000473:pathology* / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured