All the Same? The Secret Life of Prion Strains within Their Target Cells

All the Same? The Secret Life of Prion Strains within Their Target Cells
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全部都一样?

DOI:
10.3390/v11040334
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发表时间:
2019
期刊:
Viruses
影响因子:
--
通讯作者:
I. Vorberg
I. Vorberg
中科院分区:
--
文献类型:
--
作者:
I. Vorberg

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朊病毒是由错误折叠的朊蛋白(PrPSc)组成的具有传染性的富含β-薄片的蛋白质聚集体,不具有编码核酸。朊病毒通过招募并将正常细胞PrPC转化为传染性亚型进行复制。在同一宿主物种中,朊病毒毒株针对不同的大脑区域并引起不同的疾病表型。朊病毒菌株与生物物理上不同的PrPSc构象相关,这表明菌株特性在不同的PrPSc四级结构中被加密。到目前为止,还不清楚朊病毒毒株是如何靶向特定细胞并引发生产性感染的。对朊病毒生命周期的更深入的机制了解来自于允许一系列不同的朊病毒株的细胞系。尽管如此,我们仍然不知道为什么某些细胞系对一种菌株的感染有抵抗力,而对另一种菌株却有容忍度。虽然药理学和遗传学操作揭示了参与朊病毒复制的亚细胞区室,但对内吞运输途径的菌株特异性要求知之甚少。这篇综述总结了我们对朊病毒如何在其靶细胞内复制以及朊病毒细胞生物学中菌株特异性差异的了解。
Prions are infectious β-sheet-rich protein aggregates composed of misfolded prion protein (PrPSc) that do not possess coding nucleic acid. Prions replicate by recruiting and converting normal cellular PrPC into infectious isoforms. In the same host species, prion strains target distinct brain regions and cause different disease phenotypes. Prion strains are associated with biophysically distinct PrPSc conformers, suggesting that strain properties are enciphered within alternative PrPSc quaternary structures. So far it is unknown how prion strains target specific cells and initiate productive infections. Deeper mechanistic insight into the prion life cycle came from cell lines permissive to a range of different prion strains. Still, it is unknown why certain cell lines are refractory to infection by one strain but permissive to another. While pharmacologic and genetic manipulations revealed subcellular compartments involved in prion replication, little is known about strain-specific requirements for endocytic trafficking pathways. This review summarizes our knowledge on how prions replicate within their target cells and on strain-specific differences in prion cell biology.
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