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Title: Studies on the expression and function of Epstein-Barr virus encoded microRNAs in Burkitt lymphoma
Author: Amoroso, Richard Benjamin Couture
ISNI:       0000 0004 2730 6237
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2013
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Epstein-Barr virus (EBV) encodes at least 40 microRNAs (miRNAs), an important class of negative regulators that control gene expression through posttranscriptional mechanisms. However the contribution of these EBV-encoded miRNAs to the pathogenesis of virus-associated lymphomas remains poorly understood. Using newly-developed PCR assays, we first quantified the levels of viral BHRF1 and BART miRNAs in a range of EBV-positive cell lines. We show for the first time that all three BHRF1 miRNAs are abundantly expressed in Wp-restricted Burkitt lymphoma (BL) cells, but not Latency I BL cells lacking detectable Cp- or Wp-initiated EBNA transcripts. In contrast to some earlier reports, we also detected robust expression of BART miRNAs in B cell lines, although there was wide variation between individual miRNAs in a given cell. Analysis of BHRF1 and BART transcription, both in latent and lytic infection, suggested that maturation may be a key step in regulating steady-state miRNA levels. We also successfully generated lentiviral systems to express the BHRF1 miRNAs and developed reporter constructs to measure BHRF1 miRNA-dependent repression \(in\) \(vivo\). While attempts to identify BHRF1 miRNA-induced changes on the BL transcriptome were inconclusive, our data suggest that the BHRF1 miRNAs are insufficient to affect BL cell growth and cell survival.
Supervisor: Not available Sponsor: Cancer Research UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)