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| Status |
Public on Feb 03, 2014 |
| Title |
Induction of interferon-stimulated genes on the IL-4 response axis by Epstein-Barr virus infected human B cells; relevance to cellular transformation. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| 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.
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| Overall design |
9 samples were analysed and these included 3 biological replicates of the following samples: primary B cells isolated by positive selection using CD19+ Dynabeads and harvested immediately for RNA and primary B cells infected with EBV or stimulated with CD40L and IL4 and harvested 7 days post-infection/ cytokine stimulation. All biological replicates represent B cells which were pooled from 3 or 4 different buffy coat donors.
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| Contributor(s) |
Smith N, Tierney R, Wei W, Vockerodt M, Murray PG, Woodman CB, Rowe M |
| Citation(s) |
23724103 |
| Submission date |
Apr 05, 2013 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Wenbin Wei |
| E-mail(s) |
Wenbin.Wei2@durham.ac.uk
|
| Organization name |
Durham University
|
| Department |
Biosciences
|
| Street address |
Stockton Road
|
| City |
Durham |
| ZIP/Postal code |
DH1 3LE |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA196438 |
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