PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features
PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features
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DOI：
10.1128/jvi.01592-16
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发表时间：
2016-12-01
影响因子：
5.4
通讯作者：
Torres, J. M.
中科院分区：
文献类型：
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作者：
Espinosa, J. C.;Nonno, R.;Torres, J. M.
河岸田鼠是一种啮齿类动物，对不同朊病毒株的实验性传播表现出不同的易感性。在这项工作中，一组不同的朊病毒与不同的起源进行了分析，在银行田鼠表达蛋氨酸密码子109（Bv 109 M）和转基因小鼠表达生理水平的银行田鼠PrPC（BvPrP-Tg 407小鼠系）。这项工作是第一次系统的比较收集的朊病毒分离株，代表了一个面板的不同朊病毒株，在转基因小鼠模型，并在其自然对应的传输功能。结果表明，在自然物种和转基因小鼠模型中的传播特性非常相似，证明了PrP氨基酸序列在朊病毒传播易感性中的关键作用。然而，在传播的Bv 109 M和BvPrP-Tg 407的PrPSc类型的差异表明，主机因素以外的PrPC调制朊病毒株features.IMPORTANCEThe差异的敏感性银行田鼠朊病毒株可以在转基因小鼠建模，这表明这种选择性的敏感性是由田鼠PrP序列单独控制，而不是由其他物种特异性因素。在银行田鼠和转基因小鼠中朊病毒传播后观察到的表型差异表明，宿主因素以外的PrPC序列可能会影响复制的动物模型中的亚株的选择。
Bank vole is a rodent species that shows differential susceptibility to the experimental transmission of different prion strains. In this work, the transmission features of a panel of diverse prions with distinct origins were assayed both in bank vole expressing methionine at codon 109 (Bv109M) and in transgenic mice expressing physiological levels of bank vole PrPC (the BvPrP-Tg407 mouse line). This work is the first systematic comparison of the transmission features of a collection of prion isolates, representing a panel of diverse prion strains, in a transgenic-mouse model and in its natural counterpart. The results showed very similar transmission properties in both the natural species and the transgenic-mouse model, demonstrating the key role of the PrP amino acid sequence in prion transmission susceptibility. However, differences in the PrPSc types propagated by Bv109M and BvPrP-Tg407 suggest that host factors other than PrPC modulate prion strain features.IMPORTANCEThe differential susceptibility of bank voles to prion strains can be modeled in transgenic mice, suggesting that this selective susceptibility is controlled by the vole PrP sequence alone rather than by other species-specific factors. Differences in the phenotypes observed after prion transmissions in bank voles and in the transgenic mice suggest that host factors other than the PrPC sequence may affect the selection of the substrain replicating in the animal model.