Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease
Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease
复制标题
DOI：
10.1073/pnas.0305777101
复制
发表时间：
2004-03-02
影响因子：
11.1
通讯作者：
Caramelli, M
中科院分区：
文献类型：
--
作者：
Casalone, C;Zanusso, G;Caramelli, M
传染性海绵状脑病（TSE）或朊病毒病是哺乳动物神经退行性疾病，其特征在于宿主编码的细胞朊病毒蛋白（PrPC）的不溶性蛋白酶抗性同种型（PrPSc）的翻译后转化和脑蓄积。人和动物TSE因子以不同的表型存在，可以根据蛋白酶抗性PrPSc片段的分子量和糖基化程度进行生化区分。流行病学、分子和传播研究强烈表明，导致牛海绵状脑病（BSE）的单一菌株已感染人类，引起变异型克雅氏病。疯牛病病原体具有前所未有的生物学特性，它绕过了牛和人之间所谓的“物种屏障”，适应不同的哺乳动物物种，引起了人们对人类健康的极大关注。到目前为止，尚不清楚是否有一种以上的菌株可能导致牛TSE或BSE因子在自然传播后是否发生表型变异。在这里，我们提供了第二个牛TSE的证据。这种疾病的病理特征是存在PrP免疫阳性淀粉样蛋白斑块，而不是典型的BSE病例中缺乏淀粉样蛋白沉积，以及脑PrPSc积累的区域分布和拓扑结构的不同模式。此外，蛋白质印迹分析表明，PrPSc型的优势低分子量糖型和蛋白酶抗性片段的分子量低于BSE-PrPSc。引人注目的是，这种以前未描述的牛PrPSc的分子特征与散发性Creutzfeldt-Jakob病的一种不同亚型相似。
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 (PrPSc) of the host-encoded cellular prion protein (PrPC). 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 PrPSc 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 PrPSc accumulation. In addition, Western blot analysis showed a PrPSc type with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE-PrPSc. Strikingly, the molecular signature of this previously undescribed bovine PrPSc was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease.