USDA, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, 50010, USA.
Iowa State University, Department of Biomedical Sciences, Ames, 50010, USA.
Sci Rep. 2020 Feb 21;10(1):3148. doi: 10.1038/s41598-020-59819-1.
Chronic wasting disease (CWD) is a fatal, progressive disease that affects cervid species, including Rocky mountain elk (Cervus elaphus nelsoni). There are 2 allelic variants in the elk prion protein gene: L132 (leucine) and M132 (methionine). Following experimental oral challenge with the CWD agent incubation periods are longest in LL132 elk, intermediate in ML132 elk, and shortest in MM132 elk. In order to ascertain whether such CWD-infected elk carry distinct prion strains, groups of Tg12 mice that express M132 elk prion protein were inoculated intracranially with brain homogenate from individual CWD-infected elk of various genotypes (LL132, LM132, or MM132). Brain samples were examined for microscopic changes and assessment of the biochemical properties of disease-associated prion protein (PrP). On first passage, mice challenged with LL132 elk inoculum had prolonged incubation periods and greater PrP fibril stability compared to mice challenged with MM132 or LM132 inoculum. On second passage, relative incubation periods, western blot profiles, and neuropathology were maintained. These results suggest that the CWD prion isolated from LL132 elk is a novel CWD strain and that M132 PrP is able to propagate some biophysical properties of the L132 PrP conformation.
慢性消耗病（CWD）是一种致命的、进行性疾病，影响鹿科动物，包括落基山麋鹿（Cervus elaphus nelsoni）。麋鹿朊病毒蛋白基因有 2 种等位基因变异：L132（亮氨酸）和 M132（蛋氨酸）。在经过实验性口服 CWD 病原体感染后，LL132 麋鹿的潜伏期最长，ML132 麋鹿的潜伏期居中，MM132 麋鹿的潜伏期最短。为了确定感染 CWD 的麋鹿是否携带不同的朊病毒株，一组表达 M132 麋鹿朊病毒蛋白的 Tg12 小鼠通过脑内接种来自不同基因型（LL132、LM132 或 MM132）的单个感染 CWD 麋鹿的脑匀浆来接种。检查脑样本的微观变化，并评估疾病相关朊病毒蛋白（PrP）的生化特性。在初次接种时，与 MM132 或 LM132 接种物相比，用 LL132 麋鹿接种物挑战的小鼠潜伏期延长，PrP 纤维稳定性增加。在第二次接种时，相对潜伏期、Western blot 图谱和神经病理学保持不变。这些结果表明，从 LL132 麋鹿中分离出的 CWD 朊病毒是一种新型 CWD 株，M132 PrP 能够传播 L132 PrP 构象的一些生物物理特性。
