Spontaneous generation of mammalian prions
Spontaneous generation of mammalian prions
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DOI：
10.1073/pnas.1004036107
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发表时间：
2010-08-10
影响因子：
11.1
通讯作者：
Collinge, John
中科院分区：
文献类型：
--
作者：
Edgeworth, Julie A.;Gros, Nathalie;Collinge, John
朊病毒是在人类和其他哺乳动物中引起致命神经变性的传染性病原体。朊病毒热衷于与金属表面结合，如钢丝，当表面结合时，可以以惊人的效率引发大脑或培养细胞的感染。在研究金属结合朊病毒的特性时，我们使用痒病细胞实验来测量传染性，我们观察到，在低频率下，在未感染的小鼠脑匀浆涂覆金属丝的对照组中，检测结果呈阳性。这一现象在旨在排除朊病毒污染的严格和详尽的对照实验中证明是可重复的。在细胞培养中产生的传染性可以很容易地转移到小鼠身上，并且具有与实验室中使用的小鼠适应性朊病毒菌株不同的菌株特征。如果金属表面（可能带有结合的辅因子）催化正常细胞朊病毒蛋白从头生成朊病毒，则正常脑组织中明显的“自发生成”朊病毒。另外，如果朊病毒以常规方法无法检测到的水平自然存在于大脑中，金属表面可能会将它们浓缩到可以通过痒病细胞试验进行量化的程度。
Prions are transmissible agents that cause lethal neurodegeneration in humans and other mammals. Prions bind avidly to metal surfaces such as steel wires and, when surface-bound, can initiate infection of brain or cultured cells with remarkable efficiency. While investigating the properties of metal-bound prions by using the scrapie cell assay to measure infectivity, we observed, at low frequency, positive assay results in control groups in which metal wires had been coated with uninfected mouse brain homogenate. This phenomenon proved to be reproducible in rigorous and exhaustive control experiments designed to exclude prion contamination. The infectivity generated in cell culture could be readily transferred to mice and had strain characteristics distinct from the mouse-adapted prion strains used in the laboratory. The apparent "spontaneous generation" of prions from normal brain tissue could result if the metal surface, possibly with bound cofactors, catalyzed de novo formation of prions from normal cellular prion protein. Alternatively, if prions were naturally present in the brain at levels not detectable by conventional methods, metal surfaces might concentrate them to the extent that they become quantifiable by the scrapie cell assay.