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Title: Large granular lymphocyte dysregulation in malignant catarrhal fever
Author: Swa, Sandi
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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The role of virus-infected large granular lymphocytes in pathogenesis of MCF is not clear. In the absence of defined viral antigens the main objective of this study was to investigate how MCF viruses interfere with LGL proliferation and cytotoxicity. In this study, IL-2 independence and a cell surface phenotype of T/NK cells was demonstrated in most cell lines analysed. The period of survival and growth without exogenous IL-2 was variable but always exceeded that of uninfected control cells. The possible role of IL-15 (a pro-inflammatory cytokine with actions similar to IL-2) in LGL function was investigated. Results showed that IL-15 could generate and maintain the proliferative and cytotoxic phenotype of these cell lines and may be involved in the pathogenesis of MCF. The identify of specific virus proteins involved in generating the observed phenotype of the LGL cell lines had not been determined. During the course of this study, the complete genomic sequence of the A1HV-1 genome was published. Prior to this several open reading frames were detected in A1HV-1 that underwent genomic rearrangement on transition from virulence to attenuation in vitro. Thus, a final objective of this study was to determine whether these potential virulence genes are associated with the ability of LGL cell lines to transmit disease. The proteins encoded by these genes (ORF50, A6 and A7) were expressed in E. coli as recombinant proteins and used to immunise rabbits. Recombinant virus protein-specific rabbit polyclonal antibodies were generated. Using these reagents, the expression of these proteins in LGL cell lines and A1HV-1-infected monolayer cultures was investigated. The polymerase chain reaction (PCR) was used in parallel experiments to determine the presence of DNA and mRNA encoding these proteins. The results indicated that more complicated rearrangements of the A1HV-1 genome may occur on attenuation of A1HV-1 after extensive passage than has been revealed at present. However, the expression in LGL cells of proteins encoded by ORF50 and A5, that share sequence homology with the EBV R and Z transctivators, suggests that virus replication occurs in LGL cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available