IMMUNOBIOLOGY OF SCRAPIE VIRUS INFECTION

羊瘙痒症是绵羊和山羊的海绵状脑病， 实验性地传播给其他几种动物。 类似 在牛和人类中发现的疾病。 没有病原体 鉴定 然而，蛋白酶K抗性形式（PrP-res）的 内源性蛋白质命名为朊病毒蛋白（PrP）纯化， 传染性，并对疾病的发病机制很重要。 我们开发了一种敏感的PrP-res检测方法， 羊瘙痒病 基于PrP-res检测的分析更多 比目前使用的诊断方法更准确，主观性更低 基于对大脑的显微评估。 我们还发现PrP-res 脾脏或淋巴结的分析几乎与 个脑袋 我们正在确定PrP-res是否在临床前积累 淋巴结疾病。 如果是这样的话，对感染的死前测试可能 第一次可能。 我们还使用PrP-res分析来测试 以确定海绵状脑病是否 目前存在于美国牛，因此，是否有类似的流行病 在英国，BSE在美国是可能的。PrP-res分析应该 也与人类疾病对应物的诊断相关。 我们还使用了一种羊瘙痒症易感小鼠神经母细胞瘤细胞系 (MNB)研究特异性PrP基因序列对 海绵状脑病的种间传播。 为此，我们 在羊瘙痒病中表达了多种小鼠-仓鼠PrP结构， 感染的细胞，现在正在小鼠和仓鼠中分析它们， 确定物种的向性是否发生了改变。 类似的研究可以告诉我们 如果疯牛病对人类构成风险， 此外，MNB细胞以及多能胚胎癌 细胞系（P-19）被用于研究PrP的正常功能 蛋白质以及可能导致生化变化的因素 导致内源性PrP蛋白转化为PrP-res form.

Scrapie is a spongiform encephalopathy of sheep and goats which can be transmitted experimentally to several other animal species. Similar diseases are recognized in cattle and 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. Analysis 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 are determining if PrP-res accumulates prior to clinical disease in lymph node. If so, an ante mortem test for infection may for the first time be possible. We are also using PrP-res analyses to test tissues from cattle in order to determine if spongiform encephalopathy currently exists in U.S. cattle and, thereby, whether an epidemic similar to BSE in Great Britain is possible in the U.S.A. PrP-res analysis should also be relevant for diagnosis of the human disease counterparts. We are also using a scrapie-susceptible mouse neuroblastoma cell line (MNB) to study the influence which specific PrP gene sequences have on interspecies transmission of spongiform encephalopathies. To do so, we have expressed various mouse-hamster PrP constructs in the scrapie- infected cells and are now analyzing them in mice and hamsters to determine if species tropism has been altered. Similar studies could tell us if BSE represents a risk to humans. In addition, the MNB cells as well as a pluripotent embryonal carcinoma cell line (P-19) are being used to study the normal function of the PrP protein as well as factors which might account for the biochemical changes which lead to the conversion of the endogenous PrP protein to the PrP-res form.