Virus and host determinants of feline coronavirus pathogenicity

• Main Author: Porter, Emily Louise
• Published: University of Bristol 2014
• Subjects: 636.089
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.681565

Feline coronavirus (FCoV) infection is ubiquitous in multicat households in the UK. In the majority of cases, the infected cat remains healthy but a small percentage of cases develop the fatal disease of feline infectious peritonitis (FIP). This thesis describes the identification of genomic mutations that may account for the difference between the virulent and avirulent forms of FCoV. Complete FCoV genome sequences were obtained from two pairs of FCoV infected siblings, in which one of each pair died due to FIP whilst the other remained healthy. Virus-specific oligonucleotide primers were used to convert and amplify the FCo V genome RNA from each sample into cDNA fragments, which then underwent next generation sequencing. The de novo assembled genomes were compared and nucleotide differences between the genomes were identified. Thirty two nucleotide differences, which may be related to the development of FIP, were observed between the first pair of samples. The second pair of samples were found to represent only distantly related FCoV genomes. Recent evidence has suggested that one of the amino acid changes identified in this study, a methionine to leucine substitution at position 1058 in the spike protein may be associated with the development ofFIP. However, pyrosequencing analysis of a collection of well-defined clinical samples led to the conclusion that this amino acid change is linked to the tropism of the virus, rather than its ability to cause FIP. Finally, an initial step was taken towards exploring the host response to FCoV infection by comparing the levels of cellular transcripts between infected and mock infected feline cell lines. The experiments described in this thesis will help further our understanding of the roles played by the virus and the host in the pathogenesis of FCoV infections.