Studies of prion biology and diseases have elucidated several new concepts, but none was more heretical than the proposal that the biological properties that distinguish different prion strains are enciphered in the disease-causing prion protein (PrPSc). To explore this postulate, we examined the properties of PrPSc from eight prion isolates that propagate in Syrian hamster (SHa). Using resistance to protease digestion as a marker for the undenatured protein, we examined the conformational stabilities of these PrPSc molecules. All eight isolates showed sigmoidal patterns of transition from native to denatured PrPSc as a function of increasing guanidine hydrochloride (GdnHCl) concentration. Half-maximal denaturation occurred at a mean value of 1.48 M GdnHCl for the Sc237, HY, SHa(Me7), and MT-C5 isolates, all of which have ∼75-d incubation periods; a concentration of 1.08 M was found for the DY strain with a ∼170-d incubation period and ∼1.25 M for the SHa(RML) and 139H isolates with ∼180-d incubation periods. A mean value of 1.39 M GdnHCl for the Me7-H strain with a ∼320-d incubation period was found. Based on these results, the eight prion strains segregated into four distinct groups. Our results support the unorthodox proposal that distinct PrPSc conformers encipher the biological properties of prion strains.
展开▼
机译:对病毒生物学和疾病的研究阐明了几个新概念,但没有什么比在提出致病性病毒蛋白(PrP Sc sup>)中阐明区分不同病毒株的生物学特性的提议更具异端性。为了探讨这一假设,我们研究了在叙利亚仓鼠(SHa)中繁殖的8种病毒分离株的PrP Sc sup>的特性。使用对蛋白酶消化的抗性作为未变性蛋白质的标记,我们检查了这些PrP Sc sup>分子的构象稳定性。这八种分离物均显示出从天然的PrP Sc sup>到变性的S形转变,这与盐酸胍(GdnHCl)浓度的增加有关。 Sc237,HY,SHa(Me7)和MT-C5分离株的半数最大变性发生在1.48 M GdnHCl的均值上,它们均具有约75天的潜伏期。 DY菌株在约170天的潜伏期中的浓度为1.08 M,SHa(RML)和139H分离株在约180天的潜伏期的浓度为1.25M。发现Me7-H菌株的潜伏期约为320天,平均值为1.39 M GdnHCl。基于这些结果,八个病毒菌株被分为四个不同的组。我们的研究结果支持了非正统的提议,即不同的PrP Sc sup>构象异构体可以编码of病毒菌株的生物学特性。
展开▼