Post-translational changes to PrP alter transmissible spongiform encephalopathy strain properties
Post-translational changes to PrP alter transmissible spongiform encephalopathy strain properties
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DOI：
10.1038/emboj.2013.6
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发表时间：
2013-03-06
期刊：
影响因子：
11.4
通讯作者：
Manson, Jean C.
中科院分区：
文献类型：
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作者：
Cancellotti, Enrico;Mahal, Sukhvir P.;Manson, Jean C.
引起传染性海绵状脑病（TSE）或朊病毒疾病的病原体含有作为主要成分的PrPSc，这是宿主糖蛋白PrPC的异常构象异构体。TSE试剂的区别在于宿主中表型特性的差异，但宿主中可能含有具有相同氨基酸序列的PrPSc。如果PrP单独携带定义菌株特性的信息，则这些信息必须由翻译后事件编码。在这里，我们研究了宿主PrP的糖基化状态是否影响TSE菌株的特征。我们用三种TSE菌株接种野生型小鼠，这些TSE菌株通过在第一、第二或两个N-糖基化位点缺乏聚糖的PrP转基因小鼠传代。我们通过体内菌株分型和体外标准羊瘙痒病细胞试验，比较了新出现的分离株与野生型小鼠中传代的TSE菌株的感染特性。当PrPSc缺乏一种或两种聚糖时，79 A TSE菌株的菌株特异性特征发生变化。因此，TSE菌株的感染特性可以通过PrP的翻译后变化来改变，我们建议选择突变的TSE菌株。The EMBO Journal（2013）32，756-769. doi：10.1038/daj.2013.6;在线发布：2013年2月8日
The agents responsible for transmissible spongiform encephalopathies (TSEs), or prion diseases, contain as a major component PrPSc, an abnormal conformer of the host glycoprotein PrPC. TSE agents are distinguished by differences in phenotypic properties in the host, which nevertheless can contain PrPSc with the same amino-acid sequence. If PrP alone carries information defining strain properties, these must be encoded by post-translational events. Here we investigated whether the glycosylation status of host PrP affects TSE strain characteristics. We inoculated wild-type mice with three TSE strains passaged through transgenic mice with PrP devoid of glycans at the first, second or both N-glycosylation sites. We compared the infectious properties of the emerging isolates with TSE strains passaged in wild-type mice by in vivo strain typing and by the standard scrapie cell assay in vitro. Strain-specific characteristics of the 79A TSE strain changed when PrPSc was devoid of one or both glycans. Thus infectious properties of a TSE strain can be altered by post-translational changes to PrP which we propose result in the selection of mutant TSE strains. The EMBO Journal (2013) 32, 756-769. doi:10.1038/emboj.2013.6; published online: 8 February 2013