Efficient prion disease transmission through common environmental materials
Efficient prion disease transmission through common environmental materials
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DOI：
10.1074/jbc.m117.810747
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发表时间：
2018-03-02
影响因子：
4.8
通讯作者：
Soto, Claudio
中科院分区：
文献类型：
--
作者：
Pritzkow, Sandra;Morales, Rodrigo;Soto, Claudio
朊病毒病是一组致命的神经退行性疾病，与基于蛋白质的感染因子（称为朊病毒）相关。令人信服的证据表明，朊病毒疾病的自然传播是由传染性朊病毒的环境污染介导的。我们假设野生和圈养动物环境中常见的几种天然和人造材料可以结合朊病毒，并可能作为疾病传播的载体。为了验证我们的假设，我们将由各种常见环境材料（即木材、岩石、塑料、玻璃、水泥、不锈钢、铝和黄铜）组成的表面暴露于适应仓鼠的 263K 瘙痒病朊病毒，并研究了它们在体外和体内的附着和感染性保留。我们的结果表明，除了黄铜之外，这些表面可以有效地结合、保留和释放朊病毒。使用蛋白质错误折叠循环扩增技术在体外研究朊病毒复制，并通过使用受污染的植入物对脑内挑战仓鼠来分析表面结合朊病毒的感染性。我们的结果显示，几乎所有受朊病毒污染的材料都以很高的速度传播这种疾病。为了研究更自然的环境污染暴露形式，我们简单地将动物安置在由所研究的不同材料制成的大型污染球体中。引人注目的是，大多数仓鼠出现了朊病毒病的典型临床症状和典型的与疾病相关的大脑变化。我们的研究结果表明，环境中常见的表面的朊病毒污染可能是疾病传播的来源，从而扩大了我们对自然界中朊病毒传播机制的理解。
Prion diseases are a group of fatal neurodegenerative diseases associated with a protein-based infectious agent, termed prion. Compelling evidence suggests that natural transmission of prion diseases is mediated by environmental contamination with infectious prions. We hypothesized that several natural and man-made materials, commonly found in the environments of wild and captive animals, can bind prions and may act as vectors for disease transmission. To test our hypothesis, we exposed surfaces composed of various common environmental materials (i.e. wood, rocks, plastic, glass, cement, stainless steel, aluminum, and brass) to hamster-adapted 263K scrapie prions and studied their attachment and retention of infectivity in vitro and in vivo. Our results indicated that these surfaces, with the sole exception of brass, efficiently bind, retain, and release prions. Prion replication was studied in vitro using the protein mis-folding cyclic amplification technology, and infectivity of surface-bound prions was analyzed by intracerebrally challenging hamsters with contaminated implants. Our results revealed that virtually all prion-contaminated materials transmitted the disease at high rates. To investigate a more natural form of exposure to environmental contamination, we simply housed animals with large contaminated spheres made of the different materials under study. Strikingly, most of the hamsters developed classical clinical signs of prion disease and typical disease-associated brain changes. Our findings suggest that prion contamination of surfaces commonly present in the environment can be a source of disease transmission, thus expanding our understanding of the mechanisms for prion spreading in nature.