IMMUNOBIOLOGY OF SCRAPIE VIRUS INFECTION

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Scrapie is a spongiform encephalopathy which under natural conditions affects sheep and goats. Similar diseases have been described in mink, mule deer, elk, and most recently, cattle. The disease in cattle has reached epidemic proportions within Great Britain's dairy herds. At least three human diseases, Creutzfeldt-Jakob disease, Kuru, and Gerstmann-Straussler syndrome, are histologically indistinguishable from scrapie. Available evidence suggests that all of these diseases are caused by similar transmissible agents. The infectious agents which cause these diseases are particularly interesting because no nucleic acid genome has been associated with them. Interestingly, though, preparations that contain large amounts of scrapie infectivity do contain an aggregated proteinase K (PK)-resistant form of an endogenous protein, PrP. Experimental evidence suggests that PrP is important in disease pathogenesis. However, considerable controversy surrounds the exact relationship between PrP and the infectious agent of scrapie. A few investigators believe the PK-resistant form of the protein is itself the scrapie agent. Alteratively, it's possible that the protein could be a component of the agent or merely accumulate as a byproduct of disease. We have utilized scrapie-infected cell cultures which we developed to study the scrapie agent and PrP. PrP exists in two forms, PrP-sen which is found in both normal and scrapie-infected animals and is easily destroyed by exposure to PK, and PrP-res which is found only in scrapie affected animals and is partially resistant to destruction by PK. We have shown that a close association exists between the detection of PrP-res by immunoblotting and the presence of the scrapie agent. As a result we have continued to pursue the possibility that a quantitative assay for infectious agent can be developed based on dejection of PrP-res in unknown tissue culture samples. Due to the recent outbreak of bovine spongiform encephalopathy and the potential risk that infected cattle might have for humans, we have initiated studies which could lead to a more rapid method for diagnosing spongiform encephalopathies. Other studies which are underway deal with the influence of the PrP gene on the incubation period and susceptibility to scrapie, mechanisms that might explain species tropism and studies seeking to determine factors which account for the conversion of PrP-sen to PrP-res.