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Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation.
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-01-09 , DOI: 10.1093/infdis/jiz646
Juan Carlos Espinosa 1 , Alba Marín-Moreno 1 , Patricia Aguilar-Calvo 1 , Sylvie L Benestad 2 , Olivier Andreoletti 3 , Juan María Torres 1
Affiliation  

Although experimental transmission of bovine spongiform encephalopathy (BSE) to pigs and transgenic mice expressing pig cellular prion protein (PrPC) (porcine PrP [PoPrP]-Tg001) has been described, no natural cases of prion diseases in pig were reported. This study analyzed pig-PrPC susceptibility to different prion strains using PoPrP-Tg001 mice either as animal bioassay or as substrate for protein misfolding cyclic amplification (PMCA). A panel of isolates representatives of different prion strains was selected, including classic and atypical/Nor98 scrapie, atypical-BSE, rodent scrapie, human Creutzfeldt-Jakob-disease and classic BSE from different species. Bioassay proved that PoPrP-Tg001-mice were susceptible only to the classic BSE agent, and PMCA results indicate that only classic BSE can convert pig-PrPC into scrapie-type PrP (PrPSc), independently of the species origin. Therefore, conformational flexibility constraints associated with pig-PrP would limit the number of permissible PrPSc conformations compatible with pig-PrPC, thus suggesting that pig-PrPC may constitute a paradigm of low conformational flexibility that could confer high resistance to the diversity of prion strains.

中文翻译:

猪朊病毒蛋白作为对朊病毒菌株传播的有限敏感性的范例。

尽管已经描述了牛海绵状脑病 (BSE) 向猪和表达猪细胞朊病毒蛋白 (PrPC)(猪 PrP [PoPrP]-Tg001)的转基因小鼠的实验性传播,但没有报道猪中朊病毒疾病的自然病例。本研究使用 PoPrP-Tg001 小鼠作为动物生物测定法或作为蛋白质错误折叠循环扩增 (PMCA) 的底物,分析了 pig-PrPC 对不同朊病毒株的敏感性。选择了一组代表不同朊病毒株的分离株,包括经典和非典型/Nor98 痒病、非典型-疯牛病、啮齿动物痒病、人类克雅氏病和来自不同物种的经典疯牛病。生物测定证明 PoPrP-Tg001-小鼠仅对经典 BSE 病原体敏感,PMCA 结果表明只有经典 BSE 才能将猪-PrPC 转化为搔痒型 PrP (PrPSc),与物种起源无关。因此,与 pig-PrP 相关的构象灵活性限制将限制与 pig-PrPC 兼容的允许 PrPSc 构象的数量,因此表明 pig-PrPC 可能构成低构象灵活性的范例,可以赋予对朊病毒株多样性的高抗性。
更新日期:2020-01-13
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