ORA Thesis: "The evolution of viral diversity" - uuid:1d718b15-af79-4567-84ef-f97f61f75369

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Thesis

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Reference: Paul Wikramaratna, (2012). The evolution of viral diversity. DPhil. University of Oxford.

Citable link to this page: http://ora.ox.ac.uk/objects/uuid:1d718b15-af79-4567-84ef-f97f61f75369
 
Title: The evolution of viral diversity

Abstract:

This thesis focuses on the population dynamics of three antigenically diverse RNA viruses: dengue, influenza and HIV-1. It comprises a set of studies highlighting the roles of structural constraints on critical antigenic determinants, interactions between immune responses to different antigenic types, host lifespan, and the degree of mixing between different host populations in determining the epidemiology and within-host dynamics of these pathogen systems.

Dengue exists in humans as a collection of four antigenically related serotypes. Although infection by one serotype appears to convey life-long protection to homologous infection, it is believed to be a risk factor for severe disease manifestations upon secondary, heterologous infection due to the phenomenon of Antibody-Dependent Enhancement (ADE). It is not clear if third or fourth infections are possible, and if so, how they contribute to dengue epidemiology. In this thesis, I investigate the effect of third and fourth infections on the transmission dynamics of dengue.

By contrast with dengue, human influenza viruses are known to be in rapid antigenic flux, manifesting in the sequential replacement of antigenic types. This pattern of evolution does not appear to be the same in shorter-lived hosts such as swine and birds. In this thesis, I have used a simple multi-locus model to explore the relationship between host lifespan and viral evolution, as well as to elucidate the effects of transmission between hosts of different lifespan in effort to capture the cross-species element of influenza transmission.

My final chapter concerns the within-host evolution of HIV-1. I propose a new model for the pathogenesis of HIV-1 where the transition to AIDS is primarily linked to the gradual loss of the ability to make new antibody responses as the CD4+ population declines.

Together these studies emphasise that it is the changing profile of immune responses – either at the population level or within the host – that is the principal determinant of the dynamics of the pathogen, rather than the mode and tempo of antigenic innovation.


Digital Origin:Born digital
Type of Award:DPhil
Level of Award:Doctoral
Awarding Institution: University of Oxford
Notes:This thesis is not currently available via ORA.
About The Authors
institutionUniversity of Oxford
facultyMathematical,Physical & Life Sciences Division - Zoology
fundingBBSRC
 
Contributors
Prof Sunetra Gupta More by this contributor
RoleSupervisor
 
Dr Oliver G. Pybus More by this contributor
RoleSupervisor
 
Bibliographic Details
Issue Date: 2012
Copyright Date: 2012
Identifiers
Urn: uuid:1d718b15-af79-4567-84ef-f97f61f75369
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Member of collection : ora:thesis
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Copyright Holder: Paul Wikramaratna
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