Award details

Charaterisation pathogenicity and epidemiology studies on novel bocoviruses recovered from swine.

Reference	BB/F020171/1
Principal Investigator / Supervisor	Professor Gordon Allan
Co-Investigators / Co-Supervisors
Institution	Queen's University of Belfast
Department	Sch of Biological Sciences
Funding type	Research
Value (£)	346,350
Status	Completed
Type	Research Grant
Start date	01/12/2008
End date	30/11/2012
Duration	48 months

Abstract

This project aims to fully characterise 2 newly isolated swine bocoviruses and provide information on the epidemiology and pathogenicity of these viruses, Complete genomic characterisation of the swine bocavirus (SwBo) isolates will be achieved using existing methodology and a modification of a random PCR method Protein profiling of SwBo will be carried out FRET-based probe assays for faeces, blood and tissue samples will be developed for the quantitative detection of swine bocaviruses nucleic acid, and validated. Probes for ISH will be developed. Polyclonal and monoclonal antibodies to the SwBos will be prepared. Clones will be selected that cross react with all 2 isolates and, if possible, SwBo individually specific clones will also be selected for characterisation/classification of the 2 viruses. Proactive and retrospective (archived samples) studies on farms will investigate the presence of SwBo antibodies and nucleic acid/virus. The material will also be assessed for the presence of other porcine viral infections to elucidate the possible interactions of SwBos with other viruses, related to disease expression. Sera from other species will be screened for SwBo antibodies and biologicals used in the swine industry will assayed by PCR for 'contamination' with SwBo. It is expected that a number of small pilot experiments in year 1 of this project in a CD/gnotobiotic model (3 to 4 pigs per experimental infection) will be necessary, probably with at least 2 of the 3 current isolates, with and without other viruses as a co-factor. In the light of the recent findings that a 28 year old human suffering from T-non-Hodgkin Lymphoma had developed severe atypical pneumonia associated with human bocavirus infection it would be of interest to experimentally inoculate immunocompromised swine with SwBo. Additional experimental infection studies will be carried out in year 2 and 3 of the project, but their nature will depend on results generated in year 1.

Summary

Recent research in our laboratories has identified 2 new bocaviruses in swine. We have isolated these 2 viruses, which are each antigenically different, from farms in Northern Ireland with clinical postweaning multisystemic wasting syndrome (PMWS) and preliminary partial molecular characterisation of these viruses has shown that they share genetic homology with bovine parvovirus-1 (BPV-1), canine minute virus (CMV) and human bocavirus (HBoV). To date, the disease-causing significance of these novel swine bocaviruses, as primary pathogens or perhaps as immunosuppresive triggers for other infectious agents, is undetermined. Investigation of the importance of these viruses in swine and humans as potential emerging pathogens is urgently required. It is possible that these newly identified swine bocaviruses could be pathogenic to swine and may also have a zoonotic potential. Whether swine bocaviruses have implications as a debilitating primary infection in pigs and/or humans or as a contributory infection, perhaps acting as an immunosuppressive infectious agent, merits urgent investigation. This genomic sequence data of the viruses generated to date will be expanded and used to produce tools for detection of swine bocaviruses in tissue samples and blood. Monoclonal and polyclonal antibodies will be produced to all 2 new swine bocaviruses to further study the biological characterisation, epidemiology and potential pathogenesis of swine bocaviruses in swine and other species. Experimental infections of swine will be carried out to determine sites of replication of these viruses and potential pathogenesis. Archived tissue samples from diseased and non-diseaed swine (including foetal material) in the UK will be examined and prospective field studies will be carried out. The possible 'contamination' of swine biologicals, including vaccines with swine bocavirus will also be investigated. On the basis of recent findings reported for other bocaviruses (including human bocavirus) we believe that our newly discovered swine bocaviruses may have the capacity to cause respiratory infections and/or reproductive problems and/or contribute to the severity of PMWS in swine. We also hypothesise that other existing porcine viral pathogens may have an increased severity due to the presence of these new viruses. Therefore, the hypothesis to be tested is that 'newly discovered swine bocaviruses will cause respiratory and other disease scenarios in pigs and that the virus isolates will exacerbate symptoms in pigs already suffering from other disorders. Additionally an experimental model of infection with swine bocavirus could prove useful in the study of human bocavirus infections. In this project hitherto-unavailable reagents, diagnostic tests and experimental models will be developed and applied to provide information relating to the characterisation, detection, epidemiology and pathogenicity of newly discovered bocaviruses of swine. Those newly discovered isolates will be fully characterised at nucleotide level and biologically using current techniques that have already been applied in our laboratory for the discovery of other novel viral pathogens.

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Animal Health, Immunology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	Industrial Partnership Award (IPA)

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