Cellular aspects of prion replication in vitro.
Cellular aspects of prion replication in vitro.
复制标题
DOI：
10.3390/v5010374
复制
发表时间：
2013-01-22
期刊：
影响因子：
--
通讯作者：
Vorberg I
中科院分区：
文献类型：
--
作者：
Grassmann A;Wolf H;Hofmann J;Graham J;Vorberg I
朊病毒病或传染性海绵状脑病 (TSE) 是哺乳动物致命的神经退行性疾病，由主要由聚集的错误折叠朊病毒蛋白 (PrP) 组成的非常规因子引起。朊病毒通过将宿主编码的 PrP 募集到高度有序的富含 β-折叠的聚集体中进行自我繁殖。朊病毒株的临床、病理和生化特征各不相同，很可能是明显异常的朊病毒蛋白构象异构体在宿主细胞中稳定复制其交替状态的结果。了解朊病毒细胞生物学对于确定疾病干预的潜在药物靶点至关重要。许可细胞培养模型的发展极大地增强了我们对 TSE 病原体进入、繁殖和传播的了解。然而，尽管进行了广泛的研究，朊病毒感染的精确机制和潜在的菌株效应仍然是个谜。这篇综述总结了我们目前对来自细胞培养实验的细胞生物学和朊病毒繁殖的了解。我们讨论了关于细胞和病理性 PrP 运输的最新发现、异常朊病毒蛋白合成的潜在位点以及参与朊病毒进入和传播的潜在辅助因子。
Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders in mammals that are caused by unconventional agents predominantly composed of aggregated misfolded prion protein (PrP). Prions self-propagate by recruitment of host-encoded PrP into highly ordered β-sheet rich aggregates. Prion strains differ in their clinical, pathological and biochemical characteristics and are likely to be the consequence of distinct abnormal prion protein conformers that stably replicate their alternate states in the host cell. Understanding prion cell biology is fundamental for identifying potential drug targets for disease intervention. The development of permissive cell culture models has greatly enhanced our knowledge on entry, propagation and dissemination of TSE agents. However, despite extensive research, the precise mechanism of prion infection and potential strain effects remain enigmatic. This review summarizes our current knowledge of the cell biology and propagation of prions derived from cell culture experiments. We discuss recent findings on the trafficking of cellular and pathologic PrP, the potential sites of abnormal prion protein synthesis and potential co-factors involved in prion entry and propagation.