IMMUNOBIOLOGY OF SCRAPIE VIRUS INFECTION

瘙痒病是一种绵羊和山羊的海绵状脑病，可 通过实验传播给其他几种动物。多数 重要的是，牛海绵状脑病(BSE)被认为有 是从患有瘙痒病的绵羊身上获得的。类似的疾病也被认识到 在人类身上。目前还没有确定病因。然而， 一种内源性蛋白的抗蛋白酶K形式(PrP-RES) Prion蛋白(PrP)纯化具有传染性，对疾病有重要意义 发病机制。 我们开发了一种检测PrP-res的灵敏方法，并将其用于诊断 绵羊瘙痒病。基于PrP-RES检测的诊断要多得多 比目前使用的诊断方法更准确，主观性更小 基于对大脑的微观评估。我们还展示了 脾或淋巴结的PRP-RES分析几乎与 对大脑的分析。我们已经确定PrP-Res在 羊淋巴和胎盘的临床疾病。因此是在死前 羊瘙痒病的诊断是可能的。正在使用PRP-RES分析 检测牛的组织以确定海绵状 美国牛目前是否存在脑病以及是否存在一种流行病 类似于英国的疯牛病在美国是可能的。到目前为止没有 已确认阳性病例。PRP-RES分析也应 与人类疾病诊断相关的对应物。 PrP基因序列对猪瘟病毒种间传播的影响 海绵状脑病，神经元和 星形胶质细胞对疾病发病机制的影响及外周的重要性 淋巴组织对疾病的影响也在研究中。所有这些都是 利用表达仓鼠PrP(HPRP)的转基因小鼠进行研究 蛋白。HPRP在小鼠中的表达被限制为 神经元或星形胶质细胞，从而使我们能够研究每个细胞的影响 种类趋向性的类型和瘙痒病的发病机制。此外，其他小鼠 已经获得了完全不表达PrP的，并且正在被用来 研究PrP在疾病中的重要性。从这些网站获得的信息 研究应该提示可能成为目标的细胞类型或组织 最终的治疗干预。

Scrapie is a spongiform encephalopathy of sheep and goats which can be transmitted experimentally to several other animal species. Most importantly Bovine Spongiform Encephalopathy (BSE) is believed to have been acquired from sheep with scrapie. Similar diseases are recognized in humans. No etiologic agent has been identified. However, the proteinase K resistant form (PrP-res) of an endogenous protein designated prion protein (PrP) purifies with infectivity and is important to disease pathogenesis. We developed a sensitive assay for PrP-res and utilized it to diagnose scrapie in sheep. Diagnosis based on PrP-res detection was much more accurate and less subjective than the currently used method of diagnosis based on the microscopic evaluation of brain. We also showed that PrP-res analysis of spleen or lymph node was nearly as accurate as analysis of brain. We have determined that PrP-res accumulates prior to clinical disease in sheep lymph node and placenta. Thus ante-mortem diagnosis of sheep scrapie is possible. PrP-res analysis is being used to test tissues from cattle in order to determine if spongiform encephalopathy currently exists in U.S. cattle and whether an epidemic similar to BSE in Great Britain is possible in the U.S.A. So far no positive cases have been identified. PrP-res analysis should also be relevant for diagnosis of the human disease counterparts. The influence of PrP gene sequences on interspecies transmission of spongiform encephalopathies, the relative importance of neurons and astrocytes on disease pathogenesis, and the importance of peripheral lymphoid tissue on disease are also being studied. All of these investigations utilize transgenic mice which express hamster PrP (HPrP) protein. Expression of HPrP has been restricted in the mice to either neurons or astrocytes thus allowing us to study the impact of each cell type on species tropism and scrapie pathogenesis. In addition, other mice have been acquired which express no PrP at all and are being used to study the importance of PrP on disease. Information obtained from these studies should suggest cell types or tissues which might be the target of eventual therapeutic intervention.