Bessen R A, Marsh R F
Department of Veterinary Science, University of Wisconsin-Madison 53706.
J Virol. 1992 Apr;66(4):2096-101. doi: 10.1128/JVI.66.4.2096-2101.1992.
Transmissible mink encephalopathy (TME) has been transmitted to Syrian golden hamsters, and two strains of the causative agent, HYPER (HY) and DROWSY (DY), have been identified that have different biological properties. During scrapie, a TME-like disease, an endogenous cellular protein, the prion protein (PrPC), is modified (to PrPSc) and accumulates in the brain. PrPSc is partially resistant to proteases and is claimed to be an essential component of the infectious agent. Purification and analysis of PrP from hamsters infected with the HY and DY TME agent strains revealed differences in properties of PrPTME sedimentation in N-lauroylsarcosine, sensitivity to digestion with proteinase K, and migration in polyacrylamide gels. PrPC and HY PrPTME can be distinguished on the basis of their relative solubilities in detergent and protease sensitivities. PrPTME from DY-infected brain tissue shared solubility characteristics of PrP from both uninfected and HY-infected tissue. Limited protease digestion of PrPTME revealed strain-specific migration patterns upon polyacrylamide gel electrophoresis. Prolonged proteinase K treatment or N-linked deglycosylation of PrPTME did not eliminate such differences but demonstrated the PrPTME from DY-infected brain was more sensitive to protease digestion than HY PrPTME. Antigenic mapping of PrPTME with antibodies raised against synthetic peptides revealed strain-specific differences in immunoreactivity in a region of the amino-terminal end of PrPTME containing amino acid residues 89 to 103. These findings indicate that PrPTME from the two agent strains, although originating from the same host, differ in composition, conformation, or both. We conclude that PrPTME from the HY and DY strains undergo different posttranslational modifications that could explain differences in the biochemical properties of PrPTME from the two sources. Whether these strain-specific posttranslational events are directly responsible for the distinct biological properties of the HY and DY agent strains remains to be determined.
可传播水貂脑病（TME）已传播给叙利亚金仓鼠，并且已鉴定出两种具有不同生物学特性的病原体菌株，即HYPER（HY）和DROWSY（DY）。在羊瘙痒病（一种类似于TME的疾病）中，一种内源性细胞蛋白，即朊病毒蛋白（PrPC），会发生修饰（变为PrPSc）并在大脑中积累。PrPSc对蛋白酶具有部分抗性，据称是感染因子的重要组成部分。从感染HY和DY TME病原体菌株的仓鼠中纯化和分析PrP，揭示了PrPTME在月桂酰肌氨酸中的沉降特性、对蛋白酶K消化的敏感性以及在聚丙烯酰胺凝胶中的迁移存在差异。PrPC和HY PrPTME可以根据它们在去污剂中的相对溶解度和蛋白酶敏感性来区分。来自DY感染脑组织的PrPTME具有未感染和HY感染组织中PrP的共同溶解度特征。对PrPTME进行有限的蛋白酶消化后，在聚丙烯酰胺凝胶电泳上显示出菌株特异性的迁移模式。对PrPTME进行长时间的蛋白酶K处理或N-连接去糖基化并没有消除这些差异，但表明来自DY感染脑组织的PrPTME比HY PrPTME对蛋白酶消化更敏感。用针对合成肽产生的抗体对PrPTME进行抗原定位，发现在PrPTME氨基末端包含氨基酸残基89至103的区域中，免疫反应性存在菌株特异性差异。这些发现表明，来自两种病原体菌株的PrPTME尽管源自同一宿主，但在组成、构象或两者方面存在差异。我们得出结论，来自HY和DY菌株的PrPTME经历了不同的翻译后修饰，这可以解释来自两种来源的PrPTME生化特性的差异。这些菌株特异性的翻译后事件是否直接导致HY和DY病原体菌株的不同生物学特性仍有待确定。
