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The Development and application of pseudovirus based cell entry assays for emerging bat viruses

Grehan, Keith (2016) The Development and application of pseudovirus based cell entry assays for emerging bat viruses. Doctor of Philosophy (PhD) thesis, University of Kent,. (KAR id:62940)

Language: English
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Recent years have seen the emergence of two serious coronavirus pathogens with the emergence of the MERS-CoV still an ongoing concern. In addition, the recent unprecedented Ebola outbreak has claimed more than 10,000 lives and affected the lives of countless more. All three of these viruses have been linked through differing strands of research to the second largest mammalian family, Chiroptera, the bats. Bats are among the most diverse a widespread of all mammalian species and have become subject of intensive research in recent years as various bats species have been linked to a number of severe viral outbreaks. In the studies described in this thesis attempts were made to develop, pseudotyped viruses (PV) bearing the glycoprotein of a number of highly pathogenic viruses including MERS-CoV, Ebolavirus, Marburgvirus and SARS-CoV coupled with envelope-defective Human Immunodeficiency Virus and envelope-defective Murine Leukemia Virus. These tools were then used to examine the potential for cross reactivity among related coronaviruses and a number of computational tools were employed to investigate the phenomenon and attempt to develop a better understanding of the antigenic regions that are responsible for the observed cross reactivity.

The final set of experiments carried out in this thesis involved a combination of computational biology and PV based protocols to both predict patterns of viral evolution through selection analysis and to then test these predictions in the PV framework. This study lead to the generation of a number of mutant MERS-CoV spike proteins and Ebolavirus glycoproteins. These were then incorporated into the PV system and the effects of these mutations of PV production and serum neutralization were investigated.

Item Type: Thesis (Doctor of Philosophy (PhD))
Uncontrolled keywords: Chiroptera; Coronavirus; Pseudotype; Bat; MERS-CoV; Ebola; Filovirus; H17; Influenza; Zoonosis; Selective pressure; dN/dS
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 24 Aug 2017 14:12 UTC
Last Modified: 16 Feb 2021 13:48 UTC
Resource URI: (The current URI for this page, for reference purposes)
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