Feline immunodeficiency virus (FIV) is an important pathogen of domestic cats which in some cases can lead to feline AIDS. It shares many similarities with its human counterpart and is studied to understand correlates of immune-protection and mechanisms of disease progression in cats, both to improve the welfare of infected cats and as an animal model for the pathogenesis of HIV infection in humans. FIV is believed to evolve during the course of infection as a result of the error prone nature of reverse transcriptase and recombination between viral variants, but relatively little is known about this process in naturally occurring infection. Ultimately, it remains unknown why some infected cats remain healthy while others progress to AIDS rapidly. The studies reported in this thesis addressed this lack of knowledge by examining sequential blood samples obtained during the course of natural FIV infection in a population of 44 privately owned domestic cats. Employing Bayesian coalescent framework, it was demonstrated that the FIV env gene is relatively stable genetically. Although not necessary a prerequisite, this is likely to explain why many naturally infected cats can remain healthy and do not progress to AIDS. By determining the cell tropism of isolated viral variants, it was shown that sick cats were more likely to harbour viruses of the “late” phenotype than healthy animals, similar to the co-receptor switch observed during the progression of HIV infection. Intra-host diversity analyses highlighted a likely role for the leader region of the env gene in viral pathogenesis. Furthermore, recombination was demonstrated to be abundant in natural infection, indicating a requirement for the current phylogenetic classification of FIV to be revised. By assessing the strength and breadth of neutralising antibodies (NAbs), it was shown that NAbs did not appear to influence the course of natural FIV infection, arguing against a role in controlling infection and disease progression. Following an examination of samples collected from a group of privately owned Australian vaccinates, it was shown that the Fel-O-Vax FIV vaccine did not induce cross-reactive neutralising antibodies. Furthermore, in the country where commercial FIV vaccine is licenced, we identified and characterised the virus strain which was likely able to establish infection in vaccinated cat and raised concerns of vaccine’s efficacy. Overall this study broadens our understanding of natural FIV infection, and highlights that much can be learned, not from the similarities but rather by studying the differences between the feline and human lentiviruses. Such comparative studies are likely to contribute to design of highly desirable, safe and fully efficacious lentiviral vaccines.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:570023 |
| Date | January 2013 |
| Creators | Bęczkowski, Paweł |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/4186/ |
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