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Title: Examining the pathogenesis of Enterovirus 71 using human cellular models
Author: Cox, Jonathan Andrew
ISNI:       0000 0004 7428 523X
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2017
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Enterovirus 71 (EV71) is a global infectious disease that affects millions of people. The virus is the main etiological agent for hand, foot and mouth disease with outbreaks and epidemics being reported globally. Infection can cause severe neurological, cardiac and respiratory problems in children under the age of 5. Despite on-going efforts, little is known about the pathogenesis of EV71, how the host immune system responds to the virus and the molecular mechanisms behind these responses. The aims of my project are: (i) To establish an in vitro infection system to study EV71 viral kinetics to elucidate if there any difference between virus isolates that cause mild and neurotropic disease? (ii) To study the difference in infectivity and immune response in an ex vivo human blood infection system to see immune involvement plays a role in this neurotropism; (iii) To assess the ability of the different isolates to infect and cross the blood brain barrier to see if neurovirulence increases the ability to infect or cross the blood brain barrier; (iv) To study the inflammatory pathways involved in EV71 immunopathogenesis to see if the different severities of disease induce different pathways. What I found: (i) Virus isolates from patients with severe outcomes have higher levels of infectivity; (ii) Only the isolates from the most severe patients can replicate in an ex vivo PBMC system; (iii) CD4+ T Cells are the main instigators of EV71 replication in PBMCs; (iv) Severe EV71 isolates show an increased ability to disrupt the BBB; (v) IL-36g could be a involved in a novel pathway related to infection severity.
Supervisor: Ng, Lisa ; Hiscox, Julian ; Solomon, Tom Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral