From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas 77030 and.
Universidad de los Andes, Facultad de Medicina, Avenida San Carlos de Apoquindo 2200, Las Condes, Santiago 2, Chile.
J Biol Chem. 2018 Mar 2;293(9):3363-3373. doi: 10.1074/jbc.M117.810747. Epub 2018 Jan 12.
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 ( wood, rocks, plastic, glass, cement, stainless steel, aluminum, and brass) to hamster-adapted 263K scrapie prions and studied their attachment and retention of infectivity and Our results indicated that these surfaces, with the sole exception of brass, efficiently bind, retain, and release prions. Prion replication was studied using the protein misfolding 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.
朊病毒病是一组与蛋白质传染性病原体(称为朊病毒)相关的致命神经退行性疾病。令人信服的证据表明,朊病毒病的自然传播是由受传染性朊病毒污染的环境引起的。我们假设,几种天然和人造材料,通常在野生动物和圈养动物的环境中发现,可以结合朊病毒,并可能作为疾病传播的载体。为了检验我们的假设,我们将由各种常见环境材料(木材、岩石、塑料、玻璃、水泥、不锈钢、铝和黄铜)组成的表面暴露于仓鼠适应的 263K 瘙痒性朊病毒中,并研究了它们对感染性的结合和保留情况。我们的结果表明,除了黄铜,这些表面能够有效地结合、保留和释放朊病毒。使用蛋白质错误折叠循环扩增技术研究了朊病毒的复制,并通过用受污染的植入物对仓鼠进行脑内挑战来分析表面结合的朊病毒的感染性。我们的结果表明,实际上所有污染了朊病毒的材料都以高比率传播了疾病。为了研究更自然的暴露于环境污染的形式,我们只是将动物安置在由不同材料制成的大型污染球体中。令人惊讶的是,大多数仓鼠出现了朊病毒病的典型临床症状和相关的脑部变化。我们的发现表明,环境中常见的表面污染朊病毒可能是疾病传播的源头,从而扩展了我们对朊病毒在自然界中传播机制的理解。