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Title: Characterising the host response to the emerging Ebola virus, Makona variant, from West Africa
Author: Bosworth, A. J.
ISNI:       0000 0004 7659 0449
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2018
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West Africa was in the grips of an Ebola Virus Disease outbreak, caused by the emerging Makona variant of Ebola virus. High resolution molecular methods including transcriptomics and proteomics were utilised to profile the host response to the emergent Makona variant from West Africa, and compare this response with that induced by infection with other ebolaviruses, in order to identify host factors potentially important in host pathology. A comparison between Makona and other well characterised variants of Ebola virus showed that induced differences in the host response were not significant (Chapter 3) and that the transcriptomic changes were very similar to previously characterised isolates. To evaluate the importance of interferon to the lifecycle of the Makona variant, in vitro comparisons with Reston virus were performed to highlight important changes in the antiviral state of multiple cell lines during infection, this showed an effective interferon response was not a major determinant of successful ebolavirus infection (Chapter 4). The pro-inflammatory response to the Makona variant and Reston virus were compared in a relevant inflammatory cell type (Chapter 5). Analysis indicated that a highly active NFκB response may be required for efficient virus replication, indicating a potent inflammatory response is essential for the virus lifecycle (Chapter 6). The Makona variant of Ebola virus was hypothesised to induce distinctive transcriptional and proteomic changes in infected cells. In this thesis, evidence is presented that infection with the Makona variant does not induce significantly different patterns of host response from that observed in other ebolaviruses, and presents the first longitudinal transcriptomic analysis of patient infected with the Ebola virus, Makona variant. Furthermore, this study has revealed the critical role of NFκB in the lifecycle of the ebolaviruses.
Supervisor: Hiscox, Julian ; Carroll, Miles ; Hewson, Roger Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral