Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein.
Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein.
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DOI：
10.1186/s13567-022-01130-0
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发表时间：
2022-12-16
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
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慢性消耗性疾病(CWD)是一种发生在鹿、麋鹿、驯鹿和驼鹿等鹿身上的普恩病毒病。人类食用鹿角是很常见的，因此评估慢性湿疹向人类传播的风险潜力是至关重要的。在之前的研究中，我们测试了CWD通过脑内接种在过度表达人类普恩蛋白的转基因小鼠(tg66和tgrm)中的传播。用传统的Prion检测方法筛选的小鼠为阴性。然而，在通过超灵敏RT-QuIC试验筛选的88只小鼠中，我们发现了4只产生不一致阳性RT-QuIC反应的tg66小鼠。这些数据可能是假阳性反应、残留输入疫苗或暗示CWD跨物种传播到人类的亚临床感染的指示。在这个模型中，还需要进行额外的实验来了解普里恩播种活动的性质。在这份手稿中，第二次传代实验使用了来自普恩种子活性较弱的小鼠的大脑，结果表明，它们不会感染额外的受体tg66小鼠。清除实验表明，在不能复制PrPKO蛋白的tg66小鼠和PrPKO小鼠中，输入CWD的Prion种子活性在180天内被消除，表明在以后的时间点检测到的种子活性的弱阳性水平不太可能是残余接种。在连续两代后，CWD蛋白在tg66中未能致病，这表明一种强大的物种屏障阻止了CWD感染表达人Prion蛋白的小鼠。网上版载有补充材料，可在10.1186/s13567-022-01130-0查阅。
Chronic wasting disease (CWD) is a prion disease of cervids including deer, elk, reindeer, and moose. Human consumption of cervids is common, therefore assessing the risk potential of CWD transmission to humans is critical. In a previous study, we tested CWD transmission via intracerebral inoculation into transgenic mice (tg66 and tgRM) that over-expressed human prion protein. Mice screened by traditional prion detection assays were negative. However, in a group of 88 mice screened by the ultrasensitive RT-QuIC assay, we identified 4 tg66 mice that produced inconsistent positive RT-QuIC reactions. These data could be false positive reactions, residual input inoculum or indicative of subclinical infections suggestive of cross species transmission of CWD to humans. Additional experiments were required to understand the nature of the prion seeding activity in this model. In this manuscript, second passage experiments using brains from mice with weak prion seeding activity showed they were not infectious to additional recipient tg66 mice. Clearance experiments showed that input CWD prion seeding activity was eliminated by 180 days in tg66 mice and PrPKO mice, which are unable to replicate prion protein, indicating that the weak positive levels of seeding activity detected at later time points was not likely residual inoculum. The failure of CWD prions to cause disease in tg66 after two sequential passages suggested that a strong species barrier prevented CWD infection of mice expressing human prion protein. The online version contains supplementary material available at 10.1186/s13567-022-01130-0.
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DOI：
10.3390/pathogens7010005
发表时间：
2018-01-01
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
Igel-Egalon A;Béringue V;Rezaei H;Sibille P
通讯作者：
Sibille P
在没有PRP的小鼠中终生休眠后的prion增强。
影响因子：
4.8
作者：
Martin D;Reine F;Herzog L;Igel-Egalon A;Aron N;Michel C;Moudjou M;Fichet G;Quadrio I;Perret-Liaudet A;Andréoletti O;Rezaei H;Béringue V
通讯作者：
Béringue V
影响因子：
4.4
作者：
Race, Brent;Williams, Katie;Chesebro, Bruce
通讯作者：
Chesebro, Bruce
影响因子：
11.8
作者：
Miller MW;Williams ES;Hobbs NT;Wolfe LL
通讯作者：
Wolfe LL
影响因子：
2.3
作者：
Baskakov, Ilia V.
通讯作者：
Baskakov, Ilia V.