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The Pathogenesis of Foot and Mouth Disease in Pigs: Inflammatory and Antiviral Responses.

Murphy, Ciara. (2005) The Pathogenesis of Foot and Mouth Disease in Pigs: Inflammatory and Antiviral Responses. Doctoral thesis, University of Surrey (United Kingdom)..

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Foot-and-mouth disease (FMD), is caused by an Aphthovirus of the family Picornaviridae, a group of small positive-sense, single-stranded RNA viruses. FMD is one of the most contagious diseases of cloven-hoofed animals, which can be characterised by the appearance of vesicular lesions on the feet, lips and tongue. In adult sheep and goats, clinical signs can be very mild or frequently subclinical. In cattle, clinical signs are generally severe. Among domestic farm animals, the severity of disease is usually most severe in pigs and this leads one to hypothesise that the porcine host response is particularly activated by FMDV infection. The main objective of this study was to define the host response of pigs infected with FMDV to increase our understanding of the complex effects of cytokines in the tissue microenvironment and the resulting pathology. In order to achieve this objective, analysis of the induction of some antiviral cytokine mRNA, pro-inflammatory cytokine mRNA and TLR (Toll-like Receptor) mRNA at different stages of infection was carried out. A viral load study was carried out, by examining various tissues at different time points in order to describe the progression of infection in the pig. Pigs were infected with an FMDV strain collected from the UK 2001 epidemic. Groups of pigs were infected by inoculation or direct contact and compared in terms of development of clinical disease, as well as in terms of their tissue viral loads, viraemias and cytokine/TLR mRNA induction. The spread of virus in pigs was plotted based on viral loads in a number of tissues sampled at different time points from infection to severe disease. The same tissue types were then analysed for levels of antiviral cytokines, pro-inflammatory cytokines and TLR mRNAs, thus allowing a connections to be made between the behaviour of the virus and the innate antiviral and inflammatory responses of the host. Antiviral and pro-inflammatory cytokine mRNA induction occurred very early post infection and this was initially observed in the tissues and lymph nodes of the pharyngeal region as well in liver. Later, as clinical signs began to develop, further antiviral and pro-inflammatory cytokine and TLR mRNA inductions were observed in the pharyngeal region; however, mRNA induction in the tongue and skin exceeded that observed in the pharyngeal region. At this time, the tongue and skin became the major sites of viral replication and were the sites where severe clinical signs developed in the form of inflammation and vesicular lesions. While the method of infection determined the time taken for clinical signs to develop, as soon as clinical disease began its progression was the same regardless of the infection method. Clinical disease continued to increase in severity beyond the peak of viraemia and viral load, indicating that viral replication was not solely responsible for the severity disease of clinical signs. It is very likely that cytokines and TLRs contributed to this, as up-regulated levels of mRNA were observed beyond the peak of viraemia and viral load.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Murphy, Ciara.
Date : 2005
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 2005.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 14:15
Last Modified : 06 May 2020 14:18

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