Investigation of the Epstein-Barr virus’ latent to lytic cycle switch in epithelial cells suggests an interplay between host transcription co-factors and the viral early lytic cycle protein Zta.

Godfrey, Anja Katharina (2019) Investigation of the Epstein-Barr virus’ latent to lytic cycle switch in epithelial cells suggests an interplay between host transcription co-factors and the viral early lytic cycle protein Zta. Doctoral thesis (PhD), University of Sussex.

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Abstract

The Epstein-Barr virus (EBV) is one of the oldest and most successful human viruses, infecting over 95% of the human population. Exposure usually occurs during early childhood and leads to mild, or no, acute symptoms. After primary infection, the virus enters naive B cells, causing differentiation and proliferation, finally leading to lifelong persistence of the virus in these cells (latency). Infectious virions are produced during the lytic phase of the EBV life cycle, leading to spread of the virus via oral secretions. There is a strong link between EBV infection and over a dozen malignant diseases. A large amount of our EBV knowledge has been obtained in B cells. However, this virus also infects epithelial cells and is associated with a range of epithelial malignancies. This thesis aims to elucidate some of the ambiguity surrounding EBV lytic cycle in epithelial cells and to extend the knowledge surrounding the switch from latency to lytic cycle. For this purpose EBV was induced into lytic cycle, in the epithelial cell line HONE1-EBV, with the histone deacetylase inhibitor SAHA, which is used in the treatment of non-Hodgkin lymphoma and is in Phase II clinical trials for the treatment of nasopharyngeal carcinoma. The binding of the early lytic cycle protein, Zta, to the epithelial host cell genome was investigated using Chromatin Immunoprecipitation followed by high-throughput sequencing. This led to the identification of several host genes regulated by the lytic virus. In addition, results previously obtained in B cells and other public ChIP sequencing data were included in the data analysis and revealed a potentially significant role of the host transcription co-factor and protooncogene candidate BCL3. Further experiments led to the proposal of a model for the regulation of Zta gene activation involving Zta, BCL3 and TORC.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Depositing User: Library Cataloguing
Date Deposited: 11 Apr 2019 13:25
Last Modified: 12 Apr 2019 08:53
URI: http://sro.sussex.ac.uk/id/eprint/83160

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