What are the implications of genetic variation on the control of Japanese encephalitis virus?

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Bish, John L. (2024) What are the implications of genetic variation on the control of Japanese encephalitis virus? PhD thesis, University of Nottingham.

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Abstract

Japanese encephalitis virus (JEV) is a flavivirus endemic in southeast Asia, an area home to approximately 3 billion people. Infection with JEV can result in paralysis, epilepsy, and death. Currently JEV is well controlled owing to the introduction of several well-tolerated and highly efficacious vaccines.

JEV exists as five distinct genotypes which comprise a single serotype. All vaccines in use are based on genotype III. In the past twenty years the predominant genotype of JEV isolated in nature, and the cause of most human infections, has shifted from genotype III to genotype I. Research has shown that current vaccines are effective at providing antibody-based protection against a genotype I infection however concern remains over protection against genotype V.

Genotype V is the least similar compared to the other four genotypes of JEV and can deviate at the amino acid level by up to 15%. Owing to its rarity, little work has been performed on the effectiveness of vaccine derived antibodies against genotype V. Also of concern is the potential of recombinant JEV composed of heterologous genotypes. Recombination has been demonstrated experimentally within the flavivirus genus and evidence of its existence in nature has been proposed in a handful of scientific papers.

Pseudotype viruses offer an excellent opportunity to better understand the neutralisation potency of vaccine derived antibodies against the emerging genotype V. However, to date flaviviruses have remained a challenging family of viruses to pseudotype owing to several different reasons. In this thesis I describe the screening of all available JEV envelope sequences to comprehensively determine the presence of recombination in a fraction of these samples as well as the production of pseudotype JEV genotypes I, III and V. These pseudotype viruses were then used to develop a pseudotype virus neutralisation test to screen the effectiveness of vaccine derived antibodies against the different genotypes.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Daly, Janet
Rose, Nicola
Gough, Kevin
Keywords: Japanese encephalitis virus; Genotype V; Flavivirus; Envelope sequences; Recombination; Pseudotype viruses
Subjects: Q Science > QR Microbiology > QR355 Virology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Item ID: 78277
Depositing User: Bish, John
Date Deposited: 17 Jul 2024 04:40
Last Modified: 17 Jul 2024 04:40
URI: https://eprints.nottingham.ac.uk/id/eprint/78277

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