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. Preparations that contain large amounts of scrapie infectivity do contain an aggregated proteinase K (PK)-resistant form of an endogenous protein, designated PrP. The PK-resistant form of this proteins (PrP-res) is specific for diseases of the spongiform encephalopathy group. Furthermore, some experimental evidence suggests that PrP-res is important in disease pathogenesis. However, considerable controversy surrounds the exact relationship between PrP-res and the infectious agent of scrapie. A few investigators believe PrP-res is itself the scrapie agent. Alternatively, it's possible that the protein could be a component of the agent or merely accumulate as a byproduct of disease. Regardless of the relationship, detection of PrP-res offers an important tool for the study of the spongiform encephalopathies. 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 only in scrapie-affected 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. 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 deal with the influence of the PrP gene on scrapie incubation period and susceptibility, mechanisms that might explain species tropism and studies seeking to determine factors which account for the conversion of PrP-sen to PrP-res. We are also trying to identify better methods for inactivating high titered scrapie-infected tissues and surfaces.