NR AFYW
AU Jeffrey,M.J.; Begara-McGorum,I.M.; Clark,S.; Martin,S.; Clark,J.K.; Chaplin,M.J.; Gonzalez,L.
TI Occurrence and Distribution of Infection-specific PrP in Tissues of Clinical Scrapie Cases and Cull Sheep from Scrapie-affected Farms in Shetland
QU Journal of Comparative Pathology 2002 Nov; 127(4): 264-73
PT journal article
AB The prion protein (PrP) genotypes of all cull sheep originating from four scrapie-affected farms in Shetland in 1998-1999 were determined and a representative sample of the different genotypes was selected for necropsy. Samples of brain and selected viscera were removed from 159 such sheep aged 2-11 years. These samples were examined immunohistochemically and by Western blotting for infection-specific forms of PrP. None of the sheep bearing the following genotypes showed any evidence of PrP accumulation in brain, intestine, selected lymph nodes or the cranial mesenteric ganglia: ARQ/ARQ (n=41), ARQ/ARH (n=12), ARH/ARH (n=2), ARQ/ARR (n=24), ARR/ARR (n=2). In five of 71 sheep bearing a single VRQ allele, PrP accumulation was detected immunohistochemically in viscera or brain, or both. These results suggested that only a small proportion of susceptible sheep showed evidence of infection (accumulation of PrP) on the farms studied, and that even sheep of the most susceptible genotype (VRQ/VRQ) did not invariably develop disease in an infected environment. Furthermore, there was no evidence that, in sheep of semi-resistant or fully resistant genotypes, infection could be sequestered within the lymphoreticular system or peripheral nervous system and thereby provide a possible "carrier" source of infection. Rather, the data suggested that some sheep, possibly because they had been exposed to a relatively low infective dose, became infected and accumulated the infective agent over a protracted pre-clinical phase of the disease. Such sheep might be potentially infective for many years. In two VRQ/ARR genotype sheep, PrP was confined to the brain. Infection-specific PrP was also confined to the brain in two of 24 clinical cases of VRQ/ARQ scrapie. Thus, direct neuroinvasion, apparently without a prior phase of replication in the lymphoreticular system, occurred in a proportion of VRQ/ARQ sheep. Possibly it may occur in all sheep of the VRQ/ARR genotype. The factors responsible for direct neuroinvasion are not understood. However, it cannot be attributed to genotype alone.
AD Martin J. Jeffrey (m.jeffrey@vla.maff.gov.uk), Stuart Martin, Lorenzo González, VLA Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Edinburgh EH26 OPZ, Scotland, UK; Isabel M. Begara-McGorum, S. Clark, Scottish Agricultural College Veterinary Science Division, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, EH26 0PZ; J. Clark, M. Chaplin, Central Veterinary Laboratories Agency-Weybridge, Addlestone, Surrey, KT15 3NB
SP englisch
PO England