Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay
Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay
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DOI：
10.1186/s13567-019-0626-2
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发表时间：
2019-01-22
影响因子：
4.4
通讯作者：
Chesebro, Bruce
中科院分区：
文献类型：
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作者：
Race, Brent;Williams, Katie;Chesebro, Bruce
慢性消耗性疾病（CWD）是一种感染鹿、麋鹿和驼鹿的致命性朊病毒疾病。慢性消耗病首先被描述为一种消耗综合征在圈养鹿在科罗拉多和怀俄明州野生动物设施从1967年至1979年。目前，美国26个州、加拿大三个省、韩国、挪威和芬兰都报告了慢性消耗病。由于人类食用鹿科动物很常见，因此确定CWD是否会感染人类至关重要。已发表的研究，包括流行病学研究和使用动物模型（包括表达人朊蛋白的转基因小鼠）的传播研究，表明鹿慢性消耗病和人类之间存在强大的物种屏障。在目前的研究中，我们测试了CWD传输到另外两个品系的转基因小鼠（tg 66和tgRM）。这些小鼠高水平过表达人朊病毒蛋白，并且对嗜人朊病毒感染高度敏感。108只小鼠脑内接种三种不同来源的CWD。经过长时间的观察，通过RT-QuIC、免疫组织化学（IHC）和免疫印迹筛选来自接种CWD的小鼠的脑组织的朊病毒感染证据。未发现表明已发生传播的IHC或免疫印迹证据，并且大多数小鼠通过RT-QuIC测定呈阴性。然而，检测到4只小鼠具有不一致的阳性RT-QuIC反应。在这些小鼠中检测到的接种活动可能代表低水平的CWD因子，表明可能存在CWD感染的转移。或者，这些结果可能是由于假阳性反应或残留的CWD接种物。
Chronic wasting disease (CWD) is a fatal prion disease which infects deer, elk and moose. CWD was first described as a wasting syndrome in captive deer in Colorado and Wyoming wildlife facilities from 1967 to 1979. Currently, CWD has been reported in 26 states of the USA, three Canadian provinces, South Korea, Norway and Finland. Since human consumption of cervids is common, it is critical to determine if CWD can infect humans. Published research, including epidemiologic studies and transmission studies using animal models, including transgenic mice that express human prion protein, have suggested existence of a strong species barrier between cervid CWD and humans. In the current study, we tested CWD transmission into two additional strains of transgenic mice (tg66 and tgRM). These mice over-express human prion protein at high levels and are highly sensitive to infection by human-tropic prions. One hundred and eight mice were inoculated intracerebrally with three different sources of CWD. After long periods of observation, brain tissues from CWD-inoculated mice were screened for evidence of prion infection by RT-QuIC, immunohistochemistry (IHC) and immunoblot. No IHC or immunoblot evidence was found to suggest transmission had occurred, and most mice were negative by RT-QuIC assay. However, four mice with inconsistent positive RT-QuIC reactions were detected. The seeding activity detected in these mice may represent a low level of CWD agent, suggesting a possible transfer of CWD infection. Alternatively, these results might be due to false positive reactions or residual CWD inoculum.