Understanding the role of Epstein-Barr virus in T- and NK-cell disorders

George, Lindsay Clare (2016). Understanding the role of Epstein-Barr virus in T- and NK-cell disorders. University of Birmingham. Ph.D.

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Epstein-Barr virus (EBV) is associated with B- and epithelial cell malignancies. It is also associated with lymphoproliferations and malignancies of T- and natural killer (NK) cells. The global impact of these conditions is significant, and although rare, they are aggressive and are often resistant to treatment. Diagnosis is often delayed, and evidence-based treatment strategies are limited due to their rarity.
Viral gene expression in extranodal T- and NK-cell lymphoma (ENKTL), chronic active Epstein-Barr virus (CAEBV) and haemophagocytic lymphohistiocytosis (HLH) is limited. The viral latent membrane proteins LMP1, LMP2A and LMP2B-TR-TR have growth-transforming properties in B- and epithelial cells. Their effects on cellular gene expression in primary NK cells included pathways involved in cell cycle and stress responses. LMP1 and LMP2B-TR expression by ENKTL and CAEBV cell lines is associated with increased survival in the absence of relevant growth factors, but also with increased susceptibility to apoptosis. This cannot be fully explained by variation in the expression of proteins involved in the intrinsic apoptotic pathway.
Finally, we describe PrimeFlow RNA, a new protocol for identification of the EBV-infected lymphocyte subset. Importantly, this technique means that we can begin to identify druggable targets on the EBV-infected cells directly from patient blood samples.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Cancer and Genomic Sciences
Funders: Cancer Research UK, Wellcome Trust
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
URI: http://etheses.bham.ac.uk/id/eprint/6863


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