Prion Disease Unit, Division of Transboundary Animal Disease, National Institute of Animal Health (NIAH), National Agriculture and Food Research Organization (NARO), Tsukuba, Ibaraki, Japan.
Exotic Disease Research Unit, Division of Transboundary Animal Diseases, NIAH, NARO, Kodaira, Tokyo, Japan.
Vet Res. 2018 Nov 28;49(1):116. doi: 10.1186/s13567-018-0611-1.
In animal prion diseases, including bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease in cervids, and scrapie in sheep and goats, a disease-associated isoform of prion protein (PrP) accumulates in the brains of affected animals. Although the CH1641 scrapie isolate was experimentally established in the UK, a few natural CH1641-like scrapie cases have been reported in France and the UK. The molecular mass of the unglycosylated protease-resistant core of PrP (PrPres) is known to be similar between CH1641-like scrapie and experimental BSE in sheep. We previously established an experimental CH1641-like scrapie isolate (Sh294) from a natural classical scrapie case. Here, we demonstrated that the Sh294 isolate was independent of both classical and atypical BSEs by cross-species transmission to bovine PrP overexpressing (TgBoPrP) mice and wild-type mice. Interestingly, we found that the Sh294 isolate altered its host range by the transmission to TgBoPrP mice, and we succeeded in the first stable reproduction of CH1641-like scrapie specific PrPres banding patterns with the ~12-kDa small C-terminal fragment in wild-type mice. This study provides new insight into the relationship between CH1641-like scrapie isolates and BSEs. In addition, interspecies transmission models such as we have demonstrated here could be a great help to investigate the origin and host range of animal prions.
在动物朊病毒病中，包括牛海绵状脑病（BSE）、鹿慢性消耗病和绵羊和山羊的羊瘙痒病，病变相关的朊病毒蛋白（PrP）异构体在受感染动物的大脑中积累。虽然 CH1641 羊瘙痒病分离株在英国是通过实验建立的，但在法国和英国已经报道了一些自然发生的类似 CH1641 的羊瘙痒病病例。已知 CH1641 样瘙痒病和绵羊实验性 BSE 之间未糖基化的蛋白酶抗性核心 PrP（PrPres）的分子质量相似。我们之前从一个自然发生的经典瘙痒病病例中建立了一个实验性 CH1641 样瘙痒病分离株（Sh294）。在这里，我们通过将 Sh294 分离株跨物种传代到牛朊蛋白过表达（TgBoPrP）小鼠和野生型小鼠，证明了它与经典和非典型 BSE 无关。有趣的是，我们发现 Sh294 分离株通过传代到 TgBoPrP 小鼠改变了其宿主范围，并且我们成功地在野生型小鼠中首次稳定地繁殖了具有~12-kDa 小 C 端片段的 CH1641 样瘙痒病特异性 PrPres 带型。这项研究为 CH1641 样瘙痒病分离株与 BSE 之间的关系提供了新的见解。此外，我们在这里展示的这种跨物种传播模型可以极大地帮助研究动物朊病毒的起源和宿主范围。
