Protease-resistant prion protein produced in vitro lacks detectable infectivity
Protease-resistant prion protein produced in vitro lacks detectable infectivity
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DOI：
10.1099/0022-1317-80-1-11
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发表时间：
1999-01-01
影响因子：
3.8
通讯作者：
Collinge, J
中科院分区：
文献类型：
--
作者：
Hill, AF;Antoniou, M;Collinge, J
朊病毒繁殖的“仅蛋白”假说认为，感染性朊病毒由PrPSc组成，PrPSc是宿主衍生朊蛋白（PrPc）的构象异构体，与PrPc不同，PrPc对蛋白酶具有部分抗性。虽然通过在体外混合PrPSc和重组衍生PrPc产生了蛋白酶抗性PrP，但由于需要使用大量的相同物种PrPSc，因此无法进行任何新的感染性的生物测定。与传统小鼠不同，表达嵌合仓鼠-小鼠PrPC （MH2M PrPC）的转基因小鼠对Sc237仓鼠瘙痒病高度敏感。此外，它们产生MH2M PrPSc和传染性，对常规小鼠具有致病性。因此，我们尝试在体外生产MH2M PrPSc，因为所产生的任何传染性都可以与用于促进常规小鼠转化的仓鼠PrPSc区分开来。虽然产生了具有蛋白酶抗性的MH2M PrP，但在生物测定中未检测到感染性，这些结果表明PrPC获得蛋白酶抗性并不足以传播感染性。
The 'protein-only' hypothesis of prion propagation argues that infectious prions consist of PrPSc, a conformational isomer of host-derived prion protein (PrPc), which can be distinguished from PrPc by its partial resistance to proteases, While protease-resistant PrP has been produced by mixing PrPSc and recombinant-derived PrPC in vitro, bioassay of any new infectivity has been precluded by the need to use a large molar excess of same species PrPSc. Transgenic mice expressing a chimaeric hamster-mouse PrPC (MH2M PrPC) are, unlike conventional mice, highly susceptible to Sc237 hamster scrapie. In addition, they produce MH2M PrPSc and infectivity which is pathogenic for conventional mice. We have therefore attempted to produce MH2M PrPSc in vitro as any infectivity produced could be distinguished from the hamster PrPSc used to promote the conversion by bioassay in conventional mice. Although protease-resistant MH2M PrP was produced, no infectivity was detected on bioassay, These results argue that acquisition of protease resistance by PrPC is not sufficient for the propagation of infectivity.