Background Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from bovine spongiform encephalopathy (C-BSE) may co-propagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial. Methods To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens. Results No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, one isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission. Conclusions The results obtained suggest a low the zoonotic for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.

中文翻译：

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对人源化小鼠中非典型瘙痒病朊病毒人畜共患潜力的评估揭示了罕见的表型趋同，但与散发性克雅氏病朊病毒并不相同

背景 非典型/Nor98 痒病 (AS) 是一种影响绵羊和山羊的特发性传染性朊病毒病。最近的研究结果表明，来自牛海绵状脑病 (C-BSE) 的人畜共患朊病毒可能与 AS 绵羊大脑中的非典型/Nor98 朊病毒共同繁殖。调查 AS 对人类造成的风险至关重要。方法 为了评估绵羊/山羊向人类传播 AS 的风险，我们将现场和实验室分离株的脑组织连续接种到过表达人朊病毒蛋白（Met129 等位基因）的转基因小鼠中。我们研究了临床结果以及大脑和脾脏中朊病毒的存在。结果未发生初代传播，脑、脾未见临床疾病或病理性朊病毒蛋白。在随后的传代中，一种分离株逐渐适应，表现为朊病毒，其表型类似于引起人类 MM1 型散发性克雅氏病的朊病毒。然而，使用体内和体外技术的进一步表征证实这两种朊病毒剂是不同的菌株，揭示了表型趋同的情况。重要的是，这些小鼠体内没有出现 C-BSE 朊病毒，特别是在脾脏中，脾脏比大脑更容易发生 C-BSE 跨物种传播。结论 获得的结果表明 AS 的人畜共患性较低。罕见的适应可能会导致表型类似于人类自发形成的朊病毒的出现。