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Title: Pathogenesis of malignant catarrhal fever in cattle
Author: Al-Saadi, M. H.
ISNI:       0000 0004 7658 4727
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2018
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Malignant Catarrhal Fever (MCF) is a fatal disease of cattle. The principal aetiological agent is ovine herpesvirus 2 (OvHV-2). It is carried by sheep that act as an asymptomatic reservoir host. The disease is characterised by complicated pathogenesis with no preventive vaccine. Previous studies in our laboratory have shown that cattle without MCF can carry OvHV-2, indicating other factors, possibly herpesviruses are involved in MCF. Therefore, the aim of this study was to investigate OvHV-2 and other related ungulate herpesviruses. To do this, we investigate ?herpesviruses in both asymptomatic and MCF hosts by recruitment of two PCR formats (PAN-herpesvirus consensus and Real time PCR) as qualitative and quantitative approaches. The results showed for the first time that, although the related bovine herpesvirus 6 and ovine herpesvirus 1 are endemic commensals of cattle, they could afford cross-protection from infection with OvHV-2 and development MCF. OvHV-2 latency could also act a key factor in MCF-triggering. Therefore, a toolkit including antisera against OvHV-2 latency-associated nuclear antigen (oLANA) was produced in this study to demonstrate the latency in situ in cells of OvHV2-infected sheep, cattle without MCF, and cattle with MCF, using immunohistochemistry (IHC). The results demonstrated abundant OvHV-2- latency in epithelial and endothelial cells as well as leukocytes, regardless of species and disease. This finding could open new areas for the diagnosis and pathogenesis of MCF- latency. Modified vaccinia Ankara (MVA) is an attenuated virus derived from vaccinia that was developed during the smallpox eradication programme. The technology for producing recombinant MVA expressing foreign proteins is available. It has a known safety profile and recombinant MVAs expressing proteins from other pathogens are already being used as vaccines/vaccination candidates in man and other animals. We have generated MVA recombinants expressing OvHV-2 gB and gH/L as vaccine candidates for protection against the development of MCF in ungulates. These vectored-subunits generated antibodies to the native proteins after infection of mice. Therefore, they could represent logical vaccines in the future. Our results give critical insight into the pathogenesis and prevention of MCF.
Supervisor: Stewart, James ; Kipar, Anjia Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral