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。类似 牛和人类都发现了疾病。没有一种病原体有 已被确认身份。然而，蛋白酶K抗性形式(PrP-RES) 一种名为PrP的内源性蛋白可通过 传染性，在疾病发病机制中起着重要作用。 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检测的分析要多得多 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PrP- 对脾或淋巴结的RES分析几乎与分析一样准确 大脑的问题。我们还表明PrP-res在临床之前就积累了。 绵羊淋巴和胎盘的疾病。因此对绵羊的分析 胎盘或淋巴结为感染提供了一种临终检测。我们 也使用PrP-RES分析来测试牛的组织，以便 确定美国牛目前是否存在海绵状脑病 因此，类似于英国疯牛病的疫情是否 可能在美国。PRP-RES分析也应与 诊断人类疾病的同行。 特定PrP基因序列对种间传播的影响 对海绵状脑病的研究也在进行中。要做到这一点，我们有 在瘙痒病感染小鼠中表达不同的小鼠-仓鼠PrP结构 神经母细胞瘤(MNB)细胞，目前正在对它们在小鼠和 以确定物种的取向是否发生了变化。小白鼠 神经母细胞瘤细胞也被用来研究细胞的正常功能。 PrP蛋白以及确定可能导致 导致内源激素转化的生化变化 PrP蛋白与疾病相关的PrP-res形成。 类似的实验正在用转基因小鼠在体内进行。 含有仓鼠PrP基因。

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 have also shown that PrP-res accumulates prior to clinical disease in sheep lymph node and placenta. Thus analysis of sheep placenta or lymph node provides an ante mortem test for infection. 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. The influence of specific PrP gene sequences on interspecies transmission of spongiform encephalopathies is also being studied. To do so, we have expressed various mouse-hamster PrP constructs in scrapie-infected mouse neuroblastoma ( MNB ) cells and are now analyzing them in mice and hamsters to determine if species tropism has been altered. Mouse neuroblastoma cells are also being used to study the normal function of the PrP protien as well as to identify factors which might account for the biochemical changes which lead to the conversion of the endogenous PrP protein to the disease associated PrP-res form. Similar experiments are being done in vivo using transgenic mice containing the hamster PrP gene.