IMMUNOBIOLOGY OF SCRAPIE VIRUS INFECTION

瘙痒病是一种自然发生的绵羊海绵状脑病和 在临床和病理上引起与山羊相似的变化的山羊 克雅氏病和库鲁病。一种名为普里恩的独特蛋白质 蛋白质(PrP)已被发现是精制样品的主要成分 瘙痒病的传染性，一些人认为这是实际的 感染剂。我们先前分离了PrP基因的两个cdna克隆。 从被阿克帕伊病毒感染的小鼠的大脑中提取。在过去的一年里，我们完成了 确定这些小鼠蛋白cDNA的完整序列。 与仓鼠PrP的序列比较表明，这些 非常同源的基因在进化上表现出几乎相同的分歧 它们的编码区和非编码区都证实了之前的发现 PrP基因是许多物种的正常内源性基因，而不是 外源感染源的基因。有没有可能 内源性基因产物的翻译后修饰导致 尚未完全排除传染性瘙痒病病原体的产生。 尽管已经进行了几次尝试以使抓痒剂适应于 在体外生长，报道的少数阳性培养物效价很低。 尽管如此，试剂对细胞培养的适应性可以允许详细的 该试剂的表征，并提供了体外试验的可能性 滴定和生物检测相关问题的显著减少。冲向 成功地获得了小鼠来源的神经母细胞瘤细胞系 感染了瘙痒病病原体。受感染的培养保持到21岁 传代，远远超过了确保复制所需的数量 发生了。在这种来源的病原体中，感染似乎是物种特有的 未感染鼠源性神经母细胞瘤细胞 台词。来自目前受感染的培养物的细胞被克隆，希望 不断增加的传染性水平和更多的细胞系正在分析中 因为预计其他人可能会更容易接受瘙痒病 已确认身份。

Scrapie is a naturally occurring spongiform encephalopathy of sheep and goats which cause clinically 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 of scrapie infectivity and is believed by some people to be the actual infectious agent. We previously isolated two cDNA clones of the PrP mRNA from acrapie-infected mouse brain. In the past year, we have finished determining the complete sequence of these mouse prion protein cDNAs. Comparison of the sequence with that of hamster PrP indicated that these very homologous genes showed nearly equivalent evolutinary divergence in both their coding and noncoding regions which confirmed previous findings that the PrP genes are normal endogenous genes of many species rather than genes of an exogenous infectious agent. The possibility that post-translational modification of the endogenous gene product results in creation of the infectious scrapie agent has not been completely excluded. Although several attempts have been made to adapt the scrapie agent to in vitro growth, the few positive cultures reported have been of low titer. Nevertheless, adaptation of the agent to cell culture could permit detailed characterization of the agent and offer the possibility of in vitro titrations and a marked reduction in bioassay related problems. Toward this goal neuroblastoma cell lines of mouse origin were successfully infected with scrapie agent. Infected cultures were maintained through 21 passages, well beyond the number needed to assure that replication had occurred. Infection appeared to be species-specific in that agent derived from hamster brain did not infect the mouse derived neuroblastoma cell lines. Cells from currently infected cultures were cloned in hopes of increasing infectivity levels and additional cell lines are being analyzed in anticipation that others even more receptive to scrapie might be identified.