IMMUNOBIOLOGY OF SCRAPIE VIRUS INFECTION

瘙痒病是一种海绵状脑病，在自然条件下 影响绵羊和山羊。类似的疾病也在水貂、骡子中被描述过 鹿、麋鹿，最近还有牛。牛中的这种疾病已经达到 英国奶牛群中的流行比例。至少三个 人类疾病、克雅氏病、库鲁和格斯特曼-施特劳斯勒 综合征，在组织学上与瘙痒病难以区分。可用 有证据表明，所有这些疾病都是由类似的 可传播的毒剂。导致这些疾病的感染性病原体是 特别有趣的是，没有任何核酸基因组与 和他们在一起。然而，有趣的是，含有大量 的确含有一种聚集性蛋白酶K(PK)抗性 一种内源性蛋白质PrP的形式。实验证据表明PrP 在疾病发病机制中占有重要地位。然而，相当大的争议 围绕着PrP和传染性支原体之间的确切关系 瘙痒病。一些研究人员认为，这种蛋白质的PK抗性形式 本身就是抓痒病的病原体。另一种可能是，这种蛋白质 可能是试剂的一种成分，或者仅仅是作为 疾病。 我们已经使用了我们开发的感染了瘙痒病的细胞培养物来研究 瘙痒病剂和PrP。PRP以两种形式存在，PrP-Sen 在正常动物和羊痒病感染动物中都是如此，很容易被 暴露于PK和PrP-Res，这只在感染瘙痒病的动物中发现 并且部分抵抗PK的破坏。我们已经证明了收盘 免疫印迹法检测PrP-RES与 瘙痒病病原体的存在。因此，我们继续追查 对感染剂进行定量检测的可能性可以是 基于未知组织培养样品中PrP-RES的排泄而开发的。 由于最近爆发的牛海绵状脑病和 受感染的牛对人类可能有潜在的风险，我们有 启动研究，可能导致更快速的诊断方法 海绵状脑病。正在进行的其他研究涉及 PrP基因对新城疫潜伏期及易感性的影响 瘙痒病，可能解释物种取向的机制和研究寻求 确定将PrP-Sen转换为 PRP-Res。

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.