Studies on Haemopoiesis in Early Feline Immunodeficiency Virus Infection

Grant, Susan Elizabeth (1995) Studies on Haemopoiesis in Early Feline Immunodeficiency Virus Infection. PhD thesis, University of Glasgow.

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Abstract

This thesis is a study of the haematological events occurring in early experimental FIV infection in cats. In the first few weeks of infection with FIV, there is intense viral activity and viraemia. This is accompanied by lymphadenopathy, acute clinical illness and a profound neutropaenia of unknown pathogenesis. Cytopaenias of any or all of the blood cell lines are known to occur in late infection in both FIV and HIV. These are important in terms of their own morbidity and in that they limit the type and intensity of therapy which can be given to combat the viral and secondary infections. Their aetiology is likely to be multifactorial. The predictable neutropaenia seen in early FIV infection presented an ideal opportunity to elucidate the role of FIV in bone marrow. Feline haematological parameters were re-evaluated using percentile analysis of database results. Although the number of results on the database was relatively small, the advantages of the percentile system were demonstrated over the traditional "normal" ranges. A comparison between a small distinct population of research cats and cats from the general population illustrated the danger of using small groups of animals from closed populations to construct "normal" ranges, as there were distinct differences between the two groups regarding total white cell numbers, lymphocytes and eosinophils. After experimental infection with the Glasgow-8 strain of FIV, cats were sequentially blood sampled and full haematological profiles were obtained over a six month period. All infected animals developed a neutropaenia 5-6 weeks after infection. This was of variable duration and severity. Those cats with the most profound and prolonged neutropaenia were also clinically ill for a few days. The infected cats also had significantly fewer erythrocytes than control cats, although they were never anaemic. A significant difference in lymphocyte numbers was also recorded between the two groups of control and infected animals, infected animals again having lower numbers but not becoming lymphopaenic. Relative eosinopaenia was noted in infected animals. In order to establish the efficacy of neutrophil production at this time, serial bone marrow aspirates were taken from the cats and subjected to quantitative assay techniques. These assays enabled the numbers of committed neutrophil, monocyte-macrophage and erythroid precursors to be ascertained. The results showed that there were significantly fewer neutrophil and monocyte-macrophage precursors in infected cats than in control animals. This difference was most pronounced at 5-6 weeks post-infection, when the infected cats were also neutropaenic. Having demonstrated that neutrophil production in bone marrow was compromised in early FIV infection, it was then important to determine the mechanism of the progenitor cell suppression. Inhibition of neutrophil production could have been due to direct infection and killing of precursors by virus; direct infection and compromise of function of progenitor cells; or by indirect means whereby feeder, stromal or accessory cells were virally infected and growth factor regulation disrupted. Gonally-derived colonies of bone marrow cells grown in the assay system were individually screened by PCR for evidence of direct viral infection. All colony types (CFU-M, CFU-G, CFU-GM and BFU-E) were found to be positive for the FIV LTR fragment. The proportion of infected colonies varied according to time post-infection, suggesting that there was a dynamic relationship between virus, progenitors and progeny cells. Maximum numbers of infected colonies were found at 12 weeks post-infection. Immunohistochemistry was performed to investigate whether colony cells were expressing FIV proteins. Colonies from the assay plates were spun onto slides and stained with anti-p24 antibody. The vast majority of cells staining positive were macrophages. Maximum numbers of positive cells were detected at weeks 5-6 post-infection. Very few mononuclear cells stained positively, but this did not exclude the possibility of their being infected. The varying nature of the proportion of cells expressing p24 followed a similar pattern to that of the numbers being positive by PCR, reinforcing the theory that the numbers of infected cells depended on the quantity of infectious virus being produced at any one time. Peripheral neutrophils from asymptomatic long-term infected cats were screened by PCR for the presence of FIV. No virus was found in these cells. The committed precursor cells from which these cells were derived must also have been free of virus. This was to be expected of long-term infected animals in the asymptomatic stage as viral production would be at low levels, and therefore few precursors would be infected. Circulating mature cells from cats in early infection were not tested. Findings from the studies outlined above are comparable with the known facts on HIV. Further investigation into the marrow events in FIV would be useful in elucidating the pathogenesis of cytopaenias in both FIV itself and in HIV.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: David Onions
Keywords: Veterinary science, Animal diseases, Virology
Date of Award: 1995
Depositing User: Enlighten Team
Unique ID: glathesis:1995-75536
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Dec 2019 09:15
Last Modified: 19 Dec 2019 09:15
URI: http://theses.gla.ac.uk/id/eprint/75536

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