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Title: The molecular basis of malignant catarrhal fever
Author: Sharp, C. P.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Alcelaphine herpesvirus-1 (A1HV-1) is gammaherpesvirus that can cause the devastating, fatal disease malignant catarrhal fever (MCF) in susceptible ruminant hosts but not in its natural host the blue wildebeest. The purpose of this study is to characterise four unique open reading frames (ORFs) of A1HV-1 and examine their contribution to viral pathogenesis. These ORFs are located at the left hand end of the genome, a region known to contain unique transforming and immunomodulatory genes in other gammaherpesviruses, and are predicted to encode two small gene products with no significant homology to any known proteins (ORF A1 and ORF A4), a transcription factor (ORF A2) and a member of the semaphorin family (ORF A3). A 6.2 Kb fragment from A1HV-1 containing all four ORFs under their natural promoters was cloned into the left hand end region of murine gammaherpesvirus-76 (MHV-76). This allowed for the study of the in vivo contribution to pathogenesis of the gene products in a well characterised small animal model. The recombinant virus showed no difference in its ability to replicate in vitro. Viral titres and lung pathology in infected mice were also comparable although the A1HV-1 gene transcripts were detectable. The ORF A2 gene product expressed as a recombinant fusion protein in mammalian cells consistently showed nuclear localisation, supporting the prediction that this protein functions as a transcription factor. The four left hand end genes were also used to screen a novel bovine cDNA library in a yeast two-hybrid system. Analysis of the bait constructs used indicated that there is a domain or domains in the C-terminus of the ORF A2 gene product capable of interacting with DNA or DNA binding proteins, again supporting a role for this protein as a transcription factor.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available