Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD.
Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD.
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DOI：
10.1007/s00401-022-02482-9
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发表时间：
2022-10
影响因子：
12.7
通讯作者：
中科院分区：
文献类型：
--
作者：
朊病毒在哺乳动物中引起传染性和致命的神经退行性疾病。慢性消耗性疾病（CWD）是一种鹿类朊病毒病，在野生和养殖动物中广泛传播。由于慢性消耗病的发病率不断增加，慢性消耗病向人类的潜在传播日益受到关注。在这里，我们提供的证据，慢性消耗病朊病毒的人畜共患病的潜力，其可能的签名使用小鼠表达人朊蛋白（PrP）作为感染模型。这些小鼠接种鹿CWD分离株导致非典型的临床表现与朊病毒播种活性和有效的传播感染性，在大脑中，显着的是，在粪便中，但没有经典的神经病理学或蛋白质印迹表现的朊病毒疾病。有趣的是，大脑中的蛋白酶抗性PrP与家族性人类朊病毒病中发现的相似，并且在第二次传代时可传播。我们的研究结果表明，慢性消耗病可能会感染人类，虽然传输障碍可能比牛朊病毒的人畜共患传播更高。值得注意的是，我们的数据表明不同的临床表现，朊病毒签名和组织嗜性，这对当前诊断检测造成了挑战。此外，粪便中存在传染性朊病毒令人担忧，因为如果这种情况发生在人类身上，它是人与人之间传播的来源。这些发现对公共卫生和CWD管理具有重要意义。在线版本包含补充材料，可通过10.1007/s 00401 -022-02482-9获得。
Prions cause infectious and fatal neurodegenerative diseases in mammals. Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we provide evidence for a zoonotic potential of CWD prions, and its probable signature using mice expressing human prion protein (PrP) as an infection model. Inoculation of these mice with deer CWD isolates resulted in atypical clinical manifestation with prion seeding activity and efficient transmissible infectivity in the brain and, remarkably, in feces, but without classical neuropathological or Western blot appearances of prion diseases. Intriguingly, the protease-resistant PrP in the brain resembled that found in a familial human prion disease and was transmissible upon second passage. Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management. The online version contains supplementary material available at 10.1007/s00401-022-02482-9.
prion蛋白蛋白质蛋白酶敏感性，稳定性和播种活性在可变的蛋白酶敏感的prionopathy脑组织中表明分子与零星的creutzfeldt-jakob疾病重叠。
影响因子：
7.1
作者：
Peden AH;Sarode DP;Mulholland CR;Barria MA;Ritchie DL;Ironside JW;Head MW
通讯作者：
Head MW