Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed.非典型/Nor98痒病（Atypical/Nor98 scrapie）于1998年在挪威首次被发现。目前该疾病已被认定为一种全球分布的小反刍动物疫病，在欧洲检出的传染性海绵状脑病（transmissible spongiform encephalopathies, TSE）病例中占据重要比例。已有研究报道，在对牛海绵状脑病（BSE）及其他小反刍动物TSE病原体具有高度抗性的ARR/ARR型绵羊中，存在非典型/Nor98痒病感染病例。非典型/Nor98痒病病原体在其自然宿主中的生物学特性与致病机制仍不甚明晰。鉴于受感染个体的外周组织中无法检测到异常朊蛋白（PrP），该特定TSE病原体对人类和动物的暴露风险被认为处于较低水平。本研究证实，即便无法检测到异常PrP，自然感染或实验感染非典型/Nor98痒病的个体的淋巴组织、神经及肌肉中仍可积累感染性病原。研究结果表明，与其他TSE病原体相比，携带非典型/Nor98痒病感染性物质的样本可保持PrP^Sc阴性。这一特征将对现场非典型/Nor98痒病病例的检测工作造成影响，并凸显出重新评估当前该病流行率及潜在传播性评估方案的必要性。此外，本研究还对当前进入食物链的非典型/Nor98痒病和经典痒病病例外周组织中的感染性载量进行了估算。所得结果显示，人类通过膳食途径暴露于小反刍动物TSE病原体的风险，可能高于学界此前的普遍认知。