IMMUNOBIOLOGY OF SCRAPIE VIRUS INFECTION

羊瘙痒病是一种自然发生的羊海绵状脑病 引起的临床和病理变化与山羊相似 克雅二氏病和库鲁病。一种独特的 一种名为朊病毒蛋白（PrP）的蛋白质被发现是一种主要的 含有羊瘙痒病感染性的纯化样品组分， 被一些人认为是传染源 它只是 尽可能地使蛋白质作为次要物质积累， 体内疾病的产物。 为了区分这些 我们在体外研究了羊瘙痒症PrP生物合成的可能性， 感染和未感染的神经母细胞瘤细胞，使用脉冲追踪 标签实验 PrP生物合成无差异， 发现，这表明PrP在瘙痒症中的次要作用 发病机制 因为动物组织不能提供令人满意的基质 为了进行羊瘙痒病病原体的生化分析或分离，我们 继续发展和改善体外感染羊瘙痒症 我们之前描述过的细胞培养系统。 瘙痒病感染 培养物来源于单个阳性细胞，含有50- 比未克隆培养物中发现的多100倍。 通过 频率分析在扩增培养物中几乎每个细胞继续 含有羊瘙痒病病原体 细胞剂量-感染性关系如下： 研究并开发了标准曲线， 文化进行比较，从而大大减少了数量 动物需要滴定各种样品。 这些文化将 用于测试试剂纯化方法。

Scrapie is a naturally occurring spongiform encephalopathy of sheep and goats which causes clinical and pathological changes similar to those of Creutzfeld-Jakob and Kuru diseases of man. A unique protein called prion protein (PrP) has been found to be a major component of purified samples containing scrapie infectivity and is believed by some people to be the infectious agent. It is just as possible though that the protein accumulates as a secondary by- product of the disease in vivo. To discriminate between these possibilities we studied PrP biosynthesis in vitro in scrapie infected and uninfected neuroblastoma cells using pulse-chase labelling experiments. No differences in PrP biosynthesis were found, and this suggested a secondary role for PrP in scrapie pathogenesis. Because animal tissues have not provided satisfactory substrates for the biochemical analysis or isolation of the scrapie agent, we have continued to develop and improve an in vitro scrapie infected cell culture system which we described before. Scrapie infected cultures were derived from single positive cells and contained 50- 100 fold more agent than was found in uncloned cultures. By frequency analysis nearly every cell in expanded cultures continued to contain scrapie agent. Cell dose-infectivity relationships were studied and a standard curve was developed which allowed various cultures to be compared, thus significantly reducing the numbers of animals needed to titrate various samples. These cultures will be used to test methods for agent purification.