BIOCHEMICAL AND PHYSICAL-PROPERTIES OF THE PRION PROTEIN FROM 2 STRAINS OF THE TRANSMISSIBLE MINK ENCEPHALOPATHY AGENT
BIOCHEMICAL AND PHYSICAL-PROPERTIES OF THE PRION PROTEIN FROM 2 STRAINS OF THE TRANSMISSIBLE MINK ENCEPHALOPATHY AGENT
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DOI：
10.1128/jvi.66.4.2096-2101.1992
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发表时间：
1992-04-01
影响因子：
5.4
通讯作者：
MARSH, RF
中科院分区：
文献类型：
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作者：
BESSEN, RA;MARSH, RF
传染性水貂脑病（TME）已传播给叙利亚金仓鼠，已确定两种病原体HYPER （HY）和DROWSY （DY）具有不同的生物学特性。在痒病（一种tme样疾病）期间，一种内源性细胞蛋白，朊蛋白（PrP(C)）被修饰（为PrP(Sc)）并在大脑中积累。PrP(Sc))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制剂菌株的仓鼠体内纯化和分析PrP，发现PrP（TME）在n -月桂酰肌氨酸中的沉积特性、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特性存在差异。PrP(C)和HY PrP（TME）可以根据它们在洗涤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PrP（TME）与来自未感染脑组织和hy感染脑组织的PrP具有相同的溶解度特征。聚丙烯酰胺凝胶电泳显示，有限的蛋白酶消化PrP（TME）显示菌株特异性迁移模式。延长的蛋白酶K处理或n -连锁的PrP（TME）去糖基化并不能消除这种差异，但表明来自dy感染脑的PrP（TME）比HY PrP（TME）对蛋白酶消化更敏感。用针对合成肽的抗体对PrP（TME）进行抗原定位，发现PrP（TME）氨基末端含有89 ~ 103个氨基酸残基的区域的免疫反应性存在菌株特异性差异。这些结果表明，来自两种病原体菌株的PrP（TME）虽然起源于同一宿主，但在组成、构象或两者上有所不同。我们得出结论，HY和DY菌株的PrP（TME）经历了不同的翻译后修饰，这可以解释两种来源的PrP（TME）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制剂菌株的不同生物学特性仍有待确定。
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 (PrP(C)), is modified (to PrP(Sc)) and accumulates in the brain. PrP(Sc)) 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 PrP(TME) sedimentation in N-lauroylsarcosine, sensitivity to digestion with proteinase K, and migration in polyacrylamide gels. PrP(C) and HY PrP(TME) can be distinguished on the basis of their relative solubilities in detergent and protease sensitivities. PrP(TME) from DY-infected brain tissue shared solubility characteristics of PrP from both uninfected and HY-infected tissue. Limited protease digestion of PrP(TME) revealed strain-specific migration patterns upon polyacrylamide gel electrophoresis. Prolonged proteinase K treatment or N-linked deglycosylation of PrP(TME) did not eliminate such differences but demonstrated the PrP(TME) from DY-infected brain was more sensitive to protease digestion than HY PrP(TME). Antigenic mapping of PrP(TME) with antibodies raised against synthetic peptides revealed strain-specific differences in immunoreactivity in a region of the amino-terminal end of PrP(TME) containing amino acid residues 89 to 103. These findings indicate that PrP(TME) from the two agent strains, although originating from the same host, differ in composition, conformation, or both. We conclude that PrP(TME) from the HY and DY strains undergo different posttranslational modifications that could explain differences in the biochemical properties of PrP(TME) 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.