Carrier State : Do Sheep of Resistant PrP Genotypes Become Sub-Clinically Infected When Exposed to Scrapie

<p>Although PrP genotype is being used to predict susceptibility or resistance of sheep to TSEs, it is not clear whether the absence of clinical disease in resistant animals is the result of complete failure of TSEs to initiate the infection process, or whether the infection does actually become established at a low level in peripheral tissues within the animals. In order to understand the epidemiology of scrapie, it is important to differentiate between the two latter possibilities as an infected, but clinically healthy, animal represents a continuing source of infection for other sheep and also a reservoir from which new strains could emerge in the future.</p>

<p>The recent proposal to select for TSE resistance in UK sheep by breeding for high levels of the resistant ARR PrP gene allele has also raised concerns that sheep TSEs may not be eradicated by this approach but may simply disappear into sub-clinical infections and/or increase the chances of the emergence of new TSE strains with a different host range which theoretically could represent threat to human health with unknown consequences. Although ARR/ARR sheep are resistant to peripheral challenge with TSE agents, ARR/ARR sheep can support infection if the TSE is injected directly into the brain, so the possibility exists that these animals could act naturally as reservoirs of infection The main objective of this proposal is to establish whether or not resistant ARR/ARR sheep exposed for many years to natural scrapie within the NPU Cheviot flock or to experimental scrapie are able to support sub-clinical replication of the infection.</p>

<p>Infection will be detected by inoculation of body tissues into bioassay sheep of highly susceptible genotype, thus avoiding the species barrier of the mouse bioassay, and will be supported by PrPSc biochemical assays. This project is relevant to the SEAC subgroup report on Research & Surveillance for TSEs in sheep recommendation (m) carrier state. Results will allow us to develop a better understanding of the means by which TSEs spread between flocks and between sheep but will also be used to assess the long term implications of the National Scrapie Plan breeding for ARR/ARR sheep.</p>