title: Occurrence and distribution of infection-specific PrP in tissues of clinical scrapie cases and cull sheep from scrapie-affected farms in Shetland.
abstract: 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.
authors.affiliation: Veterinary Laboratories Agency-Lasswade, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, UK.
authors.forename: M
authors.initials: M
authors.lastname: Jeffrey
authors.forename: I
authors.initials: I
authors.lastname: Begara-McGorum
authors.forename: S
authors.initials: S
authors.lastname: Clark
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.forename: M
authors.initials: M
authors.lastname: Chaplin
authors.forename: L
authors.initials: L
authors.lastname: González
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D004196:Disease Outbreaks; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007124:Immunoenzyme Techniques / Q000662:veterinary; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D012608:Scrapie / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012756:Sheep; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D011328:Prions