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Aetiology pathogenesis and immunology of post-weaning multi-systemic wasting syndrome in pigs: genetic-environmental interactions

Reference	BB/E018394/1
Principal Investigator / Supervisor	Professor Dirk Werling
Co-Investigators / Co-Supervisors	Dr Theodorus Demmers, Mr John Lowe, Dr amanda nevel, Professor Dirk Pfeiffer, Professor Katharina Stark, Professor Christopher Wathes, Dr Barbara Wieland
Institution	Royal Veterinary College
Department	Pathology and Pathogen Biology
Funding type	Research
Value (£)	1,906,993
Status	Completed
Type	Research Grant
Start date	28/01/2008
End date	27/07/2013
Duration	66 months

Abstract

Post-weaning multi-systemic wasting syndrome (PMWS) is considered to be a multifactorial disease, with porcine circovirus 2 (PCV2) suggested a necessary agent. Despite the fact that infected pigs seroconvert to PCV2, it is becoming increasingly evident that PCV2 is not the sole contributor, and that the host's genetic background, environment and opportunistic pathogen(s) play a crucial role in the pathogenesis of PMWS. Interestingly, infected pigs seem to harbour PCV2 in immune cells, despite no obvious viral replication or functional differences of infected cells. Once PMWS occurs, significant changes in the subpopulations of immune cells occur. These findings in PMWS-affected pigs suggest an inability to mount an effective immune response, although the mechanism(s) by which the immune system is altered is unclear. The present proposal is in three complementary parts. First, we will identify putative secondary pathogens in a case-control study on selected farms. This epidemiological study will also identify common environmental co-factors or triggers that lead to full clinical development of PMWS. Secondly, we will identify the molecular mechanisms of pathogenesis and the early replication effects of susceptible cells by using porcine-specific microarrays on cells generated from breeds with differing in susceptibility to PMWS. We will identify signalling pathways that are altered independently of cell type. By using cells generated from different breeds, we will identify molecules/pathways that are altered in specific breeds, and will aim to combine these analyses with subsequent genetic analysis. Thirdly, despite several attempts to re-create PMWS in vivo, no consistent experimental model of PMWS has been developed. Here, using the information generated in parts 1 and 2, we will attempt to develop an in vivo model of PMWS and use it to study the aetiology of PMWS including environmental and genetic risk factors and the involvement of secondary pathogens.

Summary

Post-weaning multi-systemic wasting syndrome (PMWS) is a common disease of young pigs in the U.K. It is extremely debilitating, causes considerable suffering and poor welfare, and has a high mortality of up to 20%. The disease was first recognised in 1991 and is now prevalent worldwide. Since over 1.2 billion pigs are reared annually for human consumption, then there are good commercial and ethical reasons why new diseases like PMWS should be controlled or eliminated to ensure a safe, humane and sustainable supply of pork, sausages and ham. At first scientists thought that PMWS was caused by a virus but they now realise that genetic and environmental factors must be involved, along with opportunistic secondary pathogens. This project proposes a unique interdisciplinary approach to investigate this endemic disease and will integrate modern scientific techniques from epidemiology, genetics, microbiology, pathology, molecular immunology and environmental science to identify why PMWS occurs, leading to new control methods. British pig farmers will be heavily involved in the project, thereby guaranteeing that pigs in Britain will be the first to benefit from this research, while collaboration with a major international pharmaceutical company will ensure that new veterinary products will be made available to pig farmers worldwide.

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Animal Health, Immunology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	Combating Endemic Diseases of Farmed Animals Init (CEDFAS) [2006]
Funding Scheme	Industrial Partnership Award (IPA)

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