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

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 analyzsd 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 EBVassociated 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 EBVassociated NK/T-cell LPD.

Characterization of the Uracil-DNA Glycosylase Activity of Epstein-Barr Virus BKRF3 and Its Role in Lytic Viral DNA Replication

“…4B). These data were also in accordance with our and others' previous observation in microarray analysis that BKRF3 is expressed in the second cluster of EBV early genes (42,82,83). We then detected the expression of BKRF3 in anti-IgG-induced Akata cells and Rta-transfected Raji cells (Fig.…”

“…Here we propose that EBV BKRF3 may function in addition to LMP1 to contribute to genome instability, thus favoring AID/UNG-induced c-myc/IgH translocations. In summary, although expression of BKRF3 transcripts has been observed upon induction of EBV-positive B cells and by microarray analysis of NK/T-cell lymphoproliferative cell lines (42,82,83), we demonstrated here for the first time that BKRF3 encodes a conserved and functional uracil DNA glycosylase of the UNG family. Because inhibition of both viral and cellular UDG activities results in suppression of EBV lytic DNA replication, we suggest that BKRF3 might play an important role in EBV lytic replication, particularly in terminally differentiated cells where the cellular counterpart is absent or limited in abundance.…”

Identification and functional signature of genes regulated by structurally different ABL kinase inhibitors

“…The scanned data were normalized, verified and analysed using the Genomic Profiler software (Mitsui Knowledge Industry, Tokyo, Japan) as described previously Takaku et al, 2005;Zhang et al, 2006). First, the value was adjusted by subtraction of background fluorescence of an equivalent area.…”

Aggressive Mature Natural Killer Cell Neoplasms: from Disease Biology to Disease Manifestations

“…Other possible involved signaling pathways include those of the NOTCH (Notch homolog, translocation-associated), the NFκB (nuclear factor κB), and the WNT/ β-catenin [45,[98][99][100][101].…”