IMMUNOBIOLOGY OF SCRAPIE VIRUS INFECTION

羊瘙痒病是一种自然发生的羊海绵状脑病， 山羊引起的临床和病理变化类似于 人类的克雅二氏病和库鲁病。一种叫做朊病毒的独特蛋白质 蛋白质（PrP）已被发现是纯化样品的主要成分， 羊瘙痒病的传染性，并认为一些人是实际的 传染源 我们先前分离了两个PrP mRNA的cDNA克隆， 从被狂犬病感染的老鼠大脑中分离出来 在过去的一年里，我们完成了 确定这些小鼠朊病毒蛋白cDNA的完整序列。 与仓鼠PrP序列的比较表明，这些 非常同源基因显示出几乎相同进化趋异， 它们的编码区和非编码区都证实了以前的发现 PrP基因是许多物种的正常内源性基因，而不是 外源性感染因子的基因。 的可能性 内源基因产物的翻译后修饰导致 传染性羊瘙痒病病原体的产生尚未完全排除。 虽然已经进行了几次尝试，以适应瘙痒症的代理， 在体外生长方面，报告的少数阳性培养物的滴度较低。 尽管如此，该试剂对细胞培养的适应可以允许详细的 表征的代理，并提供在体外的可能性 滴定和生物测定相关问题的显著减少。 朝向 该目标小鼠源性神经母细胞瘤细胞系成功地 感染了羊瘙痒病病原体 感染的培养物保持21 通道，远远超出了数量需要确保复制 发生了。 感染似乎是物种特异性的，在该代理人衍生 从仓鼠脑中提取的DNA不感染小鼠源性神经母细胞瘤细胞 线 从目前感染的培养物中克隆细胞，希望 正在分析增加的感染性水平和其他细胞系 在预期中，其他人更容易接受羊瘙痒症可能是 鉴定

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.