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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 16, 2017 |
| Title |
A Mouse Model of Epstein-Barr virus LMP1 and LMP2A Driven Germinal Center B-cell Lymphoproliferative Disease |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Epstein-Barr virus (EBV) is a major cause of immunosuppression-related lymphomas. EB-driven lymphoproliferative disease complicates up to 20% of transplants, and EBV is a major cause of human immunodeficieciency virus associated lymphomas. Despite successful antiretroviral therapy, the incidence of EBV-associated Hodgkin lymphoma continues to increase in HIV+ individuals. To gain insights into EBV membrane oncoprotein effects on B-cell growth, survival and pathogenesis in vivo, we generated transgenic mouse models, in which knock-in mice transgenically express control GFP or EBV latent membrane proteins (LMP) 1 and 2A under the control of the AICDA promoter. Upon T and NK-cell depletion by antibody cocktail, LMP1 and 2A co-expression drove explosive growth of plasmablastic lymphoma-like cells, which proliferated in the spleen, caused severe end-organ damage and death. RNAseq profiling identified genome-wide LMP1 and 2A effects on B-cell gene expression, including dramatic effects on chemokine and cytokine production. While cells exhibited plasmablast features, LMP1 and 2A co-expression also induced mixed hematopoietic lineage markers, a well described but incompletely understood feature of Hodgkin lymphoma. Collectively, our results identify synergistic effects of EBV membrane oncoprotein expression, and highlight their role in lymphoproliferative diseases of immunocompromised hosts.
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| Overall design |
B220 positive B splenocytes were isolated from GFP and LMP1/2a transgenic mice, which are T/NK cell depleted by antibody cocktails, and subjected to RNA-seq analysis to compare the transcriptomic changes in LMP1/2a transgenic mice compared to GFP transgenic mice. Two mice from each transgenic group were used.
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| Contributor(s) |
Ma Y, Minamatani T, Kieff E, Kikutani H, Zhou H, Zhao B, Gewurz BE, Teruhito Y |
| Citation(s) |
28351978 |
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| Submission date |
Jan 19, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Benjamin Gewurz |
| E-mail(s) |
[email protected]
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| Organization name |
Brigham and Women's Hospital
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| Department |
Medicine
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| Street address |
181 Longwood Ave
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| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA362541 |
| SRA |
SRP097108 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE93827_LMP1_2a_vs_GFP.txt.gz |
982.0 Kb |
(ftp)(http) |
TXT |
| GSE93827_Normalized_counts.txt.gz |
666.0 Kb |
(ftp)(http) |
TXT |
| GSE93827_Raw_counts.txt.gz |
3.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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