Manuelidis Laura, Chakrabarty Trisha, Miyazawa Kohtaro, Nduom Nana-Aba, Emmerling Kaitlin
Section of Neuropathology, Yale University Medical School, 333 Cedar Street, New Haven, CT 06510, USA.
Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13529-34. doi: 10.1073/pnas.0905825106. Epub 2009 Jul 24.
Human sporadic Creutzfeldt-Jakob disease (sCJD), endemic sheep scrapie, and epidemic bovine spongiform encephalopathy (BSE) are caused by a related group of infectious agents. The new U.K. BSE agent spread to many species, including humans, and clarifying the origin, specificity, virulence, and diversity of these agents is critical, particularly because infected humans do not develop disease for many years. As with viruses, transmissible spongiform encephalopathy (TSE) agents can adapt to new species and become more virulent yet maintain fundamentally unique and stable identities. To make agent differences manifest, one must keep the host genotype constant. Many TSE agents have revealed their independent identities in normal mice. We transmitted primate kuru, a TSE once epidemic in New Guinea, to mice expressing normal and approximately 8-fold higher levels of murine prion protein (PrP). High levels of murine PrP did not prevent infection but instead shortened incubation time, as would be expected for a viral receptor. Sporadic CJD and BSE agents and representative scrapie agents were clearly different from kuru in incubation time, brain neuropathology, and lymphoreticular involvement. Many TSE agents can infect monotypic cultured GT1 cells, and unlike sporadic CJD isolates, kuru rapidly and stably infected these cells. The geographic independence of the kuru agent provides additional reasons to explore causal environmental pathogens in these infectious neurodegenerative diseases.
人类散发性克雅氏病（sCJD）、地方性绵羊瘙痒病和流行性牛海绵状脑病（BSE）是由一组相关的传染性病原体引起的。新型英国疯牛病病原体传播到了包括人类在内的许多物种，阐明这些病原体的起源、特异性、毒力和多样性至关重要，特别是因为受感染的人类多年后才会发病。与病毒一样，传染性海绵状脑病（TSE）病原体可以适应新物种并变得更具毒力，但仍保持基本独特和稳定的特性。为了使病原体差异显现出来，必须保持宿主基因型不变。许多TSE病原体已在正常小鼠中显示出其独立特性。我们将曾在新几内亚流行的一种TSE——灵长类库鲁病病原体，传播给了表达正常水平和大约高8倍水平小鼠朊病毒蛋白（PrP）的小鼠。高水平的小鼠PrP并没有阻止感染，反而缩短了潜伏期，这正如病毒受体所预期的那样。散发性克雅氏病病原体、疯牛病病原体和代表性瘙痒病病原体在潜伏期、脑海绵状病变和淋巴网状组织受累方面与库鲁病病原体明显不同。许多TSE病原体可以感染单克隆培养的GT1细胞，与散发性克雅氏病分离株不同，库鲁病病原体能快速且稳定地感染这些细胞。库鲁病病原体在地理上的独立性为探索这些传染性神经退行性疾病中的环境致病因素提供了更多理由。
