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Title: The evolution of novel subgroups of feline leukaemia virus
Author: Stewart, Hazel
ISNI:       0000 0004 2728 3063
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2013
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Feline leukaemia virus is a significant pathogen of domestic cats which causes a range of proliferative and non-proliferative haematopoietic disorders. This virus has been extensively studied in the past, however advancements in molecular techniques now allow long-standing controversial topics to be revisited and reanalysed. Although FeLV-A is the only transmittable form of the virus, FeLV-B and –C may arise in infected cats if the initial virus escapes immune clearance and establishes a chronic infection. These studies aimed to investigate previously-unanswered questions regarding FeLV pathogenesis, specifically pertaining to the ability of FeLV-A to evolve into the novel subgroups B and C. These results indicate that strains of FeLV-A possessing residues D83 and D91 in their envelope glycoprotein display increased rates of viral replication, mediated by an enhanced interaction with their cognate receptor, THTR1. Evidence is provided that these viral proteins are also able to bind efficiently to the FeLV-C receptor, FLVCR1, and that these mutations represent the first in a step-wise accumulation of mutations which eventually result in a FeLV-C viral variant emerging within the host. Subsequent studies aimed to elucidate the respective roles of the acquired immune response (neutralising antibodies) and receptor availability in driving this evolutionary process; however a definitive conclusion regarding FeLV-C selection pressures was not reached due to limitations of the model. These studies also describe the first isolation of novel FeLV-B field isolates which present without a FeLV-A co-infection. Characterisation of these strains revealed they possessed recombinant genomes, composed of exogenous LTRs and mostly endogenously-derived env genes. Further investigations into the potential functionality of endogenous FeLV elements within the domestic cat genome revealed numerous intact env genes, the proviruses of which may be restricted from exogenous transmission by their inability to form homodimeric RNA genomes with functional secondary structures. Although this suggestion requires experimental validation, this represents a novel mechanism of endogenous retroviral restriction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR355 Virology