Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman, Washington, United States of America.
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.
PLoS One. 2022 Jan 21;17(1):e0262766. doi: 10.1371/journal.pone.0262766. eCollection 2022.
Nor98-like atypical scrapie is a sporadic disease that affects the central nervous system of sheep and goats that, in contrast to classical scrapie, is not generally regarded as naturally transmissible. However, infectivity has been demonstrated via bioassay not only of brain tissue but also of certain peripheral nerves, lymphoid tissues, and muscle. This study examines placental tissue, a well characterized route of natural transmission for classical scrapie. Further, this study was conducted in sheep homozygous for the classical scrapie resistant ARR genotype and is the first to characterize the transmission of Nor98-like scrapie between homozygous-ARR sheep. Nor98-like scrapie isolated from a United States ARR/ARR sheep was transmitted to four ARR/ARR ewes via intracerebral inoculation of brain homogenate. These ewes were followed and observed to 8 years of age, remained non-clinical but exhibited progression of infection that was consistent with Nor98-like scrapie, including characteristic patterns of PrPSc accumulation in the brain and a lack of accumulation in peripheral lymphoid tissues as detected by conventional methods. Immunoblots of placental tissues from the infected ewes revealed accumulation of a distinct conformation of PrPres, particularly as the animals aged; however, the placenta showed no infectivity when analyzed via ovinized mouse bioassay. Taken together, these results support a low risk for natural transmission of Nor98-like scrapie in ARR/ARR sheep.
诺桑类似非典型羊瘙痒病是一种散发性疾病,影响绵羊和山羊的中枢神经系统,与经典羊瘙痒病不同,它通常不被认为是自然传播的。然而,通过生物测定法已经证明了传染性,不仅可以检测脑组织,还可以检测某些周围神经、淋巴组织和肌肉。本研究检查了胎盘组织,这是经典羊瘙痒病自然传播的一个特征途径。此外,本研究是在经典羊瘙痒病抗性 ARR 基因型纯合的绵羊中进行的,是首次描述 Nor98 类似羊瘙痒病在纯合-ARR 绵羊之间的传播。从美国 ARR/ARR 绵羊中分离出的 Nor98 类似羊瘙痒病通过脑匀浆的脑内接种传播给 4 只 ARR/ARR 母羊。这些母羊被跟踪观察了 8 年,仍然没有临床症状,但表现出感染的进展,这与 Nor98 类似羊瘙痒病一致,包括在大脑中积累特征性的 PrPSc 模式,以及常规方法检测到的外周淋巴组织中缺乏积累。感染母羊的胎盘组织的免疫印迹显示出一种独特构象的 PrPres 的积累,特别是随着动物年龄的增长;然而,当通过卵化小鼠生物测定法进行分析时,胎盘没有显示出感染性。综上所述,这些结果支持 Nor98 类似羊瘙痒病在 ARR/ARR 绵羊中自然传播的风险较低。