Le Dur Annick, Béringue Vincent, Andréoletti Olivier, Reine Fabienne, Laï Thanh Lan, Baron Thierry, Bratberg Bjørn, Vilotte Jean-Luc, Sarradin Pierre, Benestad Sylvie L, Laude Hubert
Virologie Immunologie Moléculaires and Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France.
Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16031-6. doi: 10.1073/pnas.0502296102. Epub 2005 Oct 20.
Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrP(c)), into a misfolded form, abnormal PrP (PrP(Sc)), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrP(Sc) detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrP(Sc) molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrP(ARR) allele (A(136)R(154)R(171)), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.
小反刍动物的羊瘙痒病属于传染性海绵状脑病（TSEs），即朊病毒病，是一类致命的神经退行性疾病，可影响人类和动物，并能通过摄入或接种在物种内部和物种之间传播。宿主编码的朊病毒蛋白（PrP），即正常细胞PrP（PrP(c)），转变为错误折叠形式的异常PrP（PrP(Sc)），在TSE传播和发病机制中起关键作用。欧盟对羊瘙痒病监测力度的加大，以及PrP(Sc)检测技术的改进，导致发现了越来越多所谓的非典型羊瘙痒病病例。这些病例包括最初在挪威绵羊中发现的具有异常病理和PrP(Sc)分子特征的临床Nor98病例，以及在目前用于大规模随机筛查屠宰或死亡动物的快速检测中产生不一致反应的“病例”。令人担忧的是，相当一部分此类病例涉及具有迄今已知对传统羊瘙痒病具有天然抗性的PrP基因型的绵羊。在此，我们报告Nor98病例和不一致病例，包括三只对抗性PrP(ARR)等位基因（A(136)R(154)R(171)）纯合的绵羊，都能有效地将疾病传播给表达羊PrP的转基因小鼠，并且它们在小鼠体内传播时具有独特的生物学和生化特征。这些观察结果支持这样一种观点，即一种直到最近才被认识到的真正具有传染性的TSE病原体感染了绵羊和山羊群体，并且可能对羊瘙痒病的控制和公共卫生具有重要意义。
