Neurobiology Division, Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Midlothian, UK.
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Turin, Italy.
J Gen Virol. 2013 Dec;94(Pt 12):2819-2827. doi: 10.1099/vir.0.052738-0. Epub 2013 Sep 17.
The transmission of bovine spongiform encephalopathy (BSE) to humans, leading to variant Creutzfeldt-Jakob disease has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health. Until recently, TSE disease in cattle was thought to be caused by a single agent strain, BSE, also known as classical BSE, or BSE-C. However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. To model the risk to human health, we previously inoculated these two forms of atypical BSE (BASE and BSE-H) into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP) (HuTg) but were unable to detect any signs of TSE pathology in these mice. However, despite the absence of TSE pathology, upon subpassage of some BASE-challenged HuTg mice, a TSE was observed in recipient gene-targeted bovine PrP Tg (Bov6) mice but not in HuTg mice. Disease transmission from apparently healthy individuals indicates the presence of subclinical BASE infection in mice expressing human PrP that cannot be identified by current diagnostic methods. However, due to the lack of transmission to HuTg mice on subpassage, the efficiency of mouse-to-mouse transmission of BASE appears to be low when mice express human rather than bovine PrP.
牛海绵状脑病（BSE）向人类的传播，导致变异型克雅氏病的发生，证明了牛传染性海绵状脑病（TSE）可能对人类健康构成威胁。直到最近，人们认为牛 TSE 病是由单一病原体株引起的，即 BSE，也称为经典 BSE 或 BSE-C。然而，由于在整个欧洲启动了一项大规模监测计划，此后发现了两种非典型 BSE 株，即牛淀粉样变性海绵状脑病（BASE，也称为 BSE-L）和 BSE-H。为了模拟对人类健康的风险，我们之前将这两种形式的非典型 BSE（BASE 和 BSE-H）接种到表达人类朊病毒蛋白（PrP）的基因靶向转基因（Tg）小鼠中（HuTg），但未能在这些小鼠中检测到任何 TSE 病理学迹象。然而，尽管没有 TSE 病理学，在一些 BASE challenged HuTg 小鼠的亚代接种后，在接受基因靶向牛 PrP Tg（Bov6）小鼠中观察到了 TSE，但在 HuTg 小鼠中没有观察到。从表现健康的个体中发现疾病的传播表明，在表达人类 PrP 的小鼠中存在亚临床 BASE 感染，但目前的诊断方法无法识别。然而，由于在亚代接种后无法将疾病传播给 HuTg 小鼠，当小鼠表达人类而非牛 PrP 时，BASE 从鼠到鼠的传播效率似乎较低。
