PRP GENOTYPE AND AGENT EFFECTS IN SCRAPIE - CHANGE IN ALLELIC INTERACTION WITH DIFFERENT ISOLATES OF AGENT IN SHEEP, A NATURAL HOST OF SCRAPIE

Man and sheep are the two species in which spongiform encephalopathies occur naturally, and in which there are recognized genetic components that predispose an individual person or sheep to clinical disease. In both species mutations/polymorphisms in the PrP gene have been linked to the incidence of natural disease, but only in sheep is it possible to investigate by deliberate exposure to infection whether these poly morphisms are directly correlated with survival time. Cheviot sheep of different PrP genotypes were challenged with one of two isolates of s crapie or an isolate of bovine spongiform encephalopathy and the survi val time and incidence of disease were monitored. Genotype analysis sh owed that dimorphisms in codons 136 and 171 of the ovine PrP gene corr elated with control of disease incidence and modulation of incubation time. Crucially, the functional effects of these domains of PrP were s hown to alternate depending on the isolate of infecting agent.