Virus Expression Database

GSE45829

Induction of interferon-stimulated genes on the IL-4 response axis by Epstein-Barr virus infected human B cells; relevance to cellular transformation.

Submitted by Wenbin Wei (University of Birmingham, United Kingdom) on Apr 05 2013

Platform: microarray – [HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]

Pubmed: 23724103

Summary Epstein-Barr virus (EBV) is an oncogenic virus that is associated with the pathogenesis of several human lymphoid malignancies, including Hodgkin's lymphoma. Infection of normal resting B cells with EBV results in activation to lymphoblasts that are phenotypically similar to those generated by physiological stimulation with CD40L plus IL-4. One important difference is that infection leads to the establishment of permanently growing lymphoblastoid cell lines, whereas CD40L/IL-4 blasts have finite proliferation life-spans. To identify early events which might later determine why EBV infected blasts go on to establish transformed cell lines, we performed global transcriptome analyses on resting B cells and on EBV and CD40L/IL-4 blasts after 7 days culture. As anticipated, there was considerable overlap in the transcriptomes of the two types of lymphoblasts when compared to the original resting B cells, reflecting common changes associated with lymphocyte activation and proliferation.
Of interest to us was a subset of 225 genes that were differentially expressed between EBV and CD40/IL4- blasts. Genes which were more highly expressed in EBV blasts were substantially and significantly enriched for a set of interferon-stimulated genes which on further in silico analyses were found to be repressed by IL-4 in other cell contexts and to be up-regulated in micro-dissected malignant cells from Hodgkin's lymphoma biopsies when compared to their normal germinal center cell counter parts. We hypothesized that EBV and IL-4 were targeting and discordantly regulating a common set of genes. This was supported experimentally in our model where IL-4 stimulation partially reversed transcriptional changes which follow EBV infection and it impaired the efficiency of EBV-induced B cell transformation. Taken together, these data suggest that discordant regulation of interferon and IL-4 pathway genes by EBV that occurs early following infection of B cells has relevance to the development or maintenance of an EBV-associated malignancy.

9 Samples

ID Title Cell Type Timepoint Reported Virus Virus Species Exclusion Reason
GSM1116241 B cells_d0_rep1 B-lymphocyte  none Uninfected
GSM1116242 B cells + EBV_d7_rep1 B-lymphocyte  7 days EBV Human gammaherpesvirus 4
GSM1116243 B cells + CD40L/IL4_d7_rep1 B-lymphocyte  7 days none Uninfected Extra interventions
CD40L & IL4 stimulated
GSM1116244 B cells_d0_rep2 B-lymphocyte  none Uninfected
GSM1116245 B cells + EBV_d7_rep2 B-lymphocyte  7 days EBV Human gammaherpesvirus 4
GSM1116246 B cells + CD40L/IL4_d7_rep2 B-lymphocyte  7 days none Uninfected Extra interventions
CD40L & IL4 stimulated
GSM1116247 B cells_d0_rep3 B-lymphocyte  none Uninfected
GSM1116248 B cells + EBV_d7_rep3 B-lymphocyte  7 days EBV Human gammaherpesvirus 4
GSM1116249 B cells + CD40L/IL4_d7_rep3 B-lymphocyte  7 days none Uninfected Extra interventions
CD40L & IL4 stimulated