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Title: African swine fever pathogenesis : comparative analysis of immunoregulatory genes in domestic and wild pigs
Author: Palgrave, Christopher J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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African swine fever virus (ASFV) causes rapid haemorrhagic death of domestic pigs and Eurasian wild boar (Sus scrofa). In contrast, native African pig species (bushpigs and warthogs) suffer only a mild, subclinical form of the infection from which they rapidly recover. In common with many other DNA viruses, ASFV has evolved a complex strategy for modulating the host-cell immune response. The ASFV-encoded protein, A238L, is known to target key sites within both the NFκB and NFAT immune-signalling pathways. Five host immunoregulatory proteins targeted or mimicked by A238L (NFAT, cyclophilin A, calcineurin A, p65(RelA) and IκBα) have been sequenced in the susceptible domestic pig, resistant warthog and phenotypically unknown babirusa. In addition, the ~1.5kbp promoter driving expression of the proinflammatory cytokine, tumour necrosis factor alpha (TNFα), has also been studied. Despite identifying high levels of nucleotide sequence conservation in these genes, polymorphisms have been identified in the NFκB subunit p65 (RelA) and the TNFα promoter, which may be of functional significance in determining the immune response characteristic of the different pig species studied. These polymorphisms have been further explored using in vitro expression and luciferase-reporter analysis in respect to a variety of stimuli. Furthermore, the identification of these sites has enabled the commercial sponsor of this project, Sygen International, to screen their domestic pig lines for ‘warthog-like’ polymorphisms, which may confer some degree of disease resistance. These findings provide a valuable insight into potential mechanisms involved in altered host susceptibility to African swine fever. In addition, this study may have wider-reaching implications for understanding issues of both susceptibility and pathogenesis relating to other infectious diseases of both humans and animals.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available