Human prion protein with valine 129 prevents expression of variant CJD phenotype
Human prion protein with valine 129 prevents expression of variant CJD phenotype
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DOI：
10.1126/science.1103932
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发表时间：
2004-12-03
期刊：
影响因子：
56.9
通讯作者：
Collinge, J
中科院分区：
文献类型：
--
作者：
Wadsworth, JDF;Asante, EA;Collinge, J
变异型克雅氏病（Variant Creutzfeldt-Jpkob disease，vCJD）是一种与牛海绵状脑病（bovine spongiform encephalopathy，BSE）样朊病毒感染相关的人类朊病毒病，具有独特的临床病理和分子表型。在这里，我们发现，在转基因小鼠中产生这种表型需要表达人朊蛋白（PrP）与蛋氨酸129。人PrP与缬氨酸129的表达导致了一个独特的表型，并显着，持久性的障碍，以传输疯牛病衍生朊病毒的传代。人朊蛋白的多态性残基129决定了不同的朊病毒株繁殖后，疯牛病朊病毒感染。因此，原发性和继发性人类感染BSE源性朊病毒可能导致散发性CJD样或新的表型，除了vCJD，这取决于朊病毒来源和受体的基因型。
Variant Creutzfeldt-jpkob disease (vCJD) is a unique and highly distinctive clinicopathological and molecular phenotype of human prion disease associated with infection with bovine spongiform encephalopathy (BSE)-like prions. Here, we found that generation of this phenotype in transgenic mice required expression of human prion protein (PrP) with methionine 129. Expression of human PrP with valine 129 resulted in a distinct phenotype and, remarkably, persistence of a barrier to transmission of BSE-derived prions on subpassage. Polymorphic residue 129 of human PrP dictated propagation of distinct prion strains after BSE prion infection. Thus, primary and secondary human infection with BSE-derived prions may result in sporadic CJD-like or novel phenotypes in addition to vCJD, depending on the genotype of the prion source and the recipient.