Casalone Cristina, Zanusso Gianluigi, Acutis Pierluigi, Ferrari Sergio, Capucci Lorenzo, Tagliavini Fabrizio, Monaco Salvatore, Caramelli Maria
Centro di Referenza Nazionale per le Encefalopatie Animali, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Bologna, 148, 10195 Turin, Italy.
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3065-70. doi: 10.1073/pnas.0305777101. Epub 2004 Feb 17.
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform (PrP(Sc)) of the host-encoded cellular prion protein (PrP(C)). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrP(Sc) fragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called "species barrier" between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrP(Sc) accumulation. In addition, Western blot analysis showed a PrP(Sc) type with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE-PrP(Sc). Strikingly, the molecular signature of this previously undescribed bovine PrP(Sc) was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease.
传染性海绵状脑病（TSEs），即朊病毒病，是哺乳动物的神经退行性疾病，其特征在于宿主编码的细胞朊蛋白（PrP(C)）发生翻译后转化并在大脑中积累不溶性、蛋白酶抗性的异构体（PrP(Sc)）。人和动物的TSE病原体以不同的表型存在，可根据蛋白酶抗性PrP(Sc)片段的分子量和糖基化程度进行生化区分。流行病学、分子和传播研究有力地表明，导致牛海绵状脑病（BSE）的单一病原体毒株已感染人类，引发了变异型克雅氏病。BSE病原体具有前所未有的生物学特性，它跨越了牛和人之间所谓的“物种屏障”并适应不同的哺乳动物物种，这引起了人们对人类健康的极大关注。迄今为止，尚不清楚是否有不止一种毒株导致牛TSE，或者BSE病原体在自然传播后是否会发生表型变异。在此，我们提供了第二种牛TSE的证据。该疾病的病理特征是存在PrP免疫阳性淀粉样斑块，这与典型BSE病例中缺乏淀粉样沉积相反，并且脑PrP(Sc)积累的区域分布和拓扑模式也不同。此外，蛋白质印迹分析显示一种PrP(Sc)类型，其低分子量糖型占优势，且蛋白酶抗性片段的分子量低于BSE-PrP(Sc)。令人惊讶的是，这种先前未描述的牛PrP(Sc)的分子特征与散发性克雅氏病的一个独特亚型中遇到的特征相似。
