Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Prog Mol Biol Transl Sci. 2020;175:179-211. doi: 10.1016/bs.pmbts.2020.08.009. Epub 2020 Sep 8.
The transmission of prions between species is typically an inefficient process due to the species barrier, which represents incompatibility between prion seed and substrate molecules. Bank voles (Myodes glareolus) are an exception to this rule, as they are susceptible to a diverse range of prion strains from many different animal species. In particular, bank voles can be efficiently infected with most types of human prions and have played a critical role in validating variably protease-sensitive prionopathy (VPSPr) and certain forms of Gerstmann-Sträussler-Scheinker (GSS) disease as bona fide prion disorders rather than non-transmissible proteinopathies. The bank vole prion protein (BVPrP) confers a "universal prion acceptor" phenotype when expressed in mice and when used as a substrate for in vitro prion amplification assays, indicating that the unique prion transmission properties of bank voles are mediated by BVPrP. Over-expression of BVPrP in mice can also promote the spontaneous development of prion disease, indicating that BVPrP is intrinsically prone to both spontaneous and template-directed misfolding. Here, we discuss the utility of bank voles and BVPrP for prion research and how they have provided new tools for establishing rapid animal bioassays, modeling spontaneous prion disease, standardizing prion diagnostics, and understanding the molecular basis of the species barrier.
物种间朊病毒的传播通常是低效的，这是由于物种屏障的存在，这代表了朊病毒种子与基质分子之间的不兼容性。田鼠（Myodes glareolus）是这一规则的例外，因为它们容易受到来自许多不同动物物种的多种朊病毒株的感染。特别是，田鼠可以有效地感染大多数类型的人类朊病毒，并且在验证可变蛋白酶敏感的朊病毒病（VPSPr）和某些形式的格斯特曼-施特劳斯勒-谢因克（GSS）病作为真正的朊病毒疾病而不是不可传播的蛋白病方面发挥了关键作用。当在小鼠中表达和用作体外朊病毒扩增测定的基质时，田鼠朊病毒蛋白（BVPrP）赋予“通用朊病毒接受体”表型，表明田鼠独特的朊病毒传播特性是由 BVPrP 介导的。在小鼠中过度表达 BVPrP 也可以促进朊病毒病的自发发展，表明 BVPrP 本身容易自发和模板指导的错误折叠。在这里，我们讨论了田鼠和 BVPrP 在朊病毒研究中的应用，以及它们如何为建立快速动物生物测定、模拟自发性朊病毒病、标准化朊病毒诊断以及理解物种屏障的分子基础提供了新的工具。
