Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease
Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease
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DOI：
10.1093/emboj/19.17.4425
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发表时间：
2000-09-01
期刊：
影响因子：
11.4
通讯作者：
Caughey, B
中科院分区：
文献类型：
--
作者：
Raymond, GJ;Bossers, A;Caughey, B
慢性消耗性疾病（CWD）是鹿和麋鹿的一种传染性海绵状脑病（TSE），其对其他物种的传染性知之甚少。控制种际间TSE易感性的重要因素是源种和受种/基因型之间的朊病毒蛋白（PrP）同源性。此外，一个物种的蛋白酶抗性PrP （PrP-res）诱导另一个物种的正常PrP （PrP-sen）在体外转化为蛋白酶抗性状态的效率与TSE病原体的跨物种传播率有关。本研究表明，奶牛的CWD相关PrP-res （PrPCWD）很容易诱导重组奶牛PrP-sen分子转化为蛋白酶抗性状态，这与已知的CWD在奶牛之间的传播性一致，相比之下，PrPCWD诱导的人类和牛PrP-sen的转化效率要低得多，而绵羊PrP-sen的转化则处于中间状态。这些结果表明，在分子水平上存在一种屏障，可以限制这些非宫颈物种对CWD的易感性。
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and elk, and little is known about its transmissibility to other species. An important factor controlling interspecies TSE susceptibility is prion protein (PrP) homology between the source and recipient species/genotypes. Furthermore, the efficiency with which the protease-resistant PrP (PrP-res) of one species induces the in vitro conversion of the normal PrP (PrP-sen) of another species to the protease-resistant state correlates with the cross-species transmissibility of TSE agents. Here we show that the CWD-associated PrP-res (PrPCWD) of cervids readily induces the conversion of recombinant cervid PrP-sen molecules to the protease-resistant state in accordance with the known transmissibility of CWD between cervids, In contrast, PrPCWD-induced conversions of human and bovine PrP-sen were much less efficient, and conversion of ovine PrP-sen was intermediate. These results demonstrate a barrier at the molecular level that should limit the susceptibility of these non-cervid species to CWD.