Moore R A, Vorberg I, Priola S A
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Arch Virol Suppl. 2005(19):187-202. doi: 10.1007/3-211-29981-5_15.
Transmissible spongiform encephalopathies (TSEs or prion diseases) are neurological disorders associated with the aggregation of a pathologic isoform of a host-encoded protein, termed prion protein (PrP). The pathologic isoform of PrP, termed PrP(Sc), is a major constituent of the infectious agent. TSE diseases are characterized by neurodegenerative failure and inevitable morbidity. Bovine spongiform encephalopathy (BSE) has been transmitted from cattle to humans to cause a new variant of Creutzfeldt-Jakob syndrome. The potential for chronic wasting disease to similarly cross the species barrier from cervids to humans is considered unlikely but possible. Thus, understanding how TSE agents overcome resistance to transmission between species is crucial if we are to prevent future epidemics. The species barrier usually can be abrogated to varying degrees in laboratory animals. Studies done with transgenic animals, tissue culture, and cell-free assays established PrP as being necessary for TSE pathogenesis and illustrated that certain amino acid residues are more influential than others for conferring resistance to TSE agent transmission. The essence of what constitutes a TSE agent's species compatibility is thought to be orchestrated by a complex interplay of contributions from its primary amino acid sequence, its glycoform patterns, and its three-dimensional structure.
传染性海绵状脑病（TSEs或朊病毒病）是与宿主编码蛋白（称为朊病毒蛋白，PrP）的病理性异构体聚集相关的神经疾病。PrP的病理性异构体，称为PrP(Sc)，是感染因子的主要成分。TSE疾病的特征是神经退行性衰竭和不可避免的发病。牛海绵状脑病（BSE）已从牛传播给人类，导致了新型克雅氏综合征。慢性消耗性疾病从鹿科动物跨物种传播给人类的可能性虽被认为不大但仍有可能。因此，如果我们要预防未来的流行病，了解TSE病原体如何克服物种间传播的阻力至关重要。在实验动物中，物种屏障通常可以在不同程度上被消除。利用转基因动物、组织培养和无细胞检测进行的研究确定PrP是TSE发病机制所必需的，并表明某些氨基酸残基在赋予对TSE病原体传播的抗性方面比其他残基更具影响力。人们认为，构成TSE病原体物种兼容性的本质是由其一级氨基酸序列、糖型模式和三维结构的复杂相互作用所精心安排的。
