Abstract:
Chronic wasting disease (CWD), a prion disease affecting cervids, has been known in North America (NA) since the 1960s and emerged in Norway in 2016. Surveillance and studies have revealed that there are different forms of CWD in Fennoscandia: contagious CWD in Norwegian reindeer and sporadic CWD in moose and red deer. Experimental studies have demonstrated that NA CWD prions can infect various species, but thus far, there have been no reports of natural transmission to non-cervid species. In vitro and laboratory animal studies of the Norwegian CWD strains suggest that these strains are different from the NA strains. In this work, we describe the intracerebral transmission of reindeer CWD to six scrapie-susceptible sheep. Detection methods included immunohistochemistry (IHC), western blot (WB), enzyme-linked immunosorbent assay (ELISA), real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA). In the brain, grey matter vacuolation was limited, while all sheep exhibited vacuolation of the white matter. IHC and WB conventional detection techniques failed to detect prions; however, positive seeding activity with the RT-QuIC and PMCA amplification techniques was observed in the central nervous system of all but one sheep. Prions were robustly amplified in the lymph nodes of all animals, mainly by RT-QuIC. Additionally, two lymph nodes were positive by WB, and one was positive by ELISA. These findings suggest that sheep can propagate reindeer CWD prions after intracerebral inoculation, resulting in an unusual disease phenotype and prion distribution with a low amount of detectable prions.
摘要:
慢性消耗性疾病(CWD),一种影响宫颈的朊病毒病,自1960年代以来一直在北美(NA)闻名,并于2016年在挪威出现。监测和研究表明,芬诺斯坎迪亚有不同形式的CWD:挪威驯鹿的传染性CWD和驼鹿和马鹿的零星CWD。实验研究表明,NACWD病毒可以感染各种物种,但是到目前为止,没有自然传播到非宫颈物种的报道。挪威CWD菌株的体外和实验室动物研究表明,这些菌株与NA菌株不同。在这项工作中,我们描述了驯鹿CWD向六只易感瘙痒的绵羊的脑内传播。检测方法包括免疫组织化学(IHC),蛋白质印迹(WB),酶联免疫吸附测定(ELISA),实时震颤诱导转化(RT-QuIC)和蛋白质错误折叠循环扩增(PMCA)。在大脑中,灰质空泡是有限的,而所有绵羊都表现出白质的液泡化。IHC和WB常规检测技术未能检测到朊病毒;然而,用RT-QuIC和PMCA扩增技术在除一只绵羊以外的所有绵羊的中枢神经系统中观察到阳性播种活性。朊病毒在所有动物的淋巴结中都强烈扩增,主要由RT-QuIC。此外,两个淋巴结WB阳性,ELISA检测结果为阳性。这些发现表明,绵羊可以在脑内接种后繁殖驯鹿CWD病毒,导致异常的疾病表型和朊病毒分布,可检测到的朊病毒数量很少。