Tranulis Michael A, Benestad Sylvie L, Baron Thierry, Kretzschmar Hans
Norwegian School of Veterinary Science, Oslo, Norway.
Top Curr Chem. 2011;305:23-50. doi: 10.1007/128_2011_161.
Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrP(Sc)), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans.
尽管诸如人类克雅氏病（CJD）和绵羊瘙痒病等朊病毒疾病早已为人所知，但我们对其流行病学和发病机制的了解仍处于早期阶段。漫长的潜伏期以及缺乏监测和鉴定这些病原体的有效方法阻碍了研究进展。朊病毒蛋白（PrP）的抗蛋白酶异构体，即所谓的“瘙痒病形式”（PrP(Sc)），被用作疾病标志物，并用于分类学目的，与临床、病理和遗传数据相关联。在人类中，朊病毒疾病可散发出现（散发性克雅氏病，sCJD）或由遗传因素引起（遗传性克雅氏病，gCJD等），由PrP基因（PRNP）突变导致，或通过食源性感染，牛海绵状脑病（BSE）病原体导致变异型克雅氏病（vCJD）。人类朊病毒疾病的人际传播仅在食人行为（巴布亚新几内亚的库鲁病）或通过医疗或外科治疗（医源性克雅氏病，iCJD）后才被知晓。相比之下，小型反刍动物的瘙痒病和鹿类的慢性消耗病（CWD）在这些物种中表现为传染病。然而，最近在绵羊中发现了所谓的非典型朊病毒疾病形式（非典型/挪威98型瘙痒病），在牛中发现了BSE-H和BSE-L。这些疾病类似于散发性或遗传性人类朊病毒疾病，可能是其动物对应物。这一假设也引发了一个重大的公共卫生问题，即这些疾病与其人类对应疾病之间可能存在的流行病学联系。
