The evolution of novel subgroups of feline leukaemia virus

Stewart, Hazel (2013) The evolution of novel subgroups of feline leukaemia virus. PhD thesis, University of Glasgow.

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Abstract

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.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QR Microbiology > QR355 Virology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Supervisor's Name: Willett, Prof. Brian
Date of Award: 2013
Depositing User: Dr Hazel Stewart
Unique ID: glathesis:2013-3799
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 07 Jan 2013 13:52
Last Modified: 09 Jan 2013 10:53
URI: http://theses.gla.ac.uk/id/eprint/3799

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