The Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
PLoS One. 2024 Nov 7;19(11):e0312837. doi: 10.1371/journal.pone.0312837. eCollection 2024.
Prion diseases are transmissible, fatal neurologic diseases of mammals caused by the accumulation of mis-folded, disease associated prion protein (PrPd). Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease and can occur by sporadic onset (sCJD) (~85% of CJD cases), genetic mutations in the prion protein gene (10-15%) or iatrogenic transmission (rare). PrPd is difficult to inactivate and many methods to reduce prion infectivity are dangerous, caustic, expensive, or impractical. Identifying viable and safe methods for decontamination of CJD exposed materials is critically important for medical facilities and research institutions. Previous research has shown that concentrated sodium hypochlorite (bleach) was effective at inactivation of CJD prions derived from brains of mice or guinea pigs. Unfortunately, human prions adapted to rodents may mis-fold differently than in humans, and the rodent adapted prions may not have the same resistance or susceptibility to inactivation present in bona fide CJD prions. To confirm that bleach was efficacious against human sourced CJD prions, we exposed different subtypes of sCJD-infected human brain homogenates to different concentrations of bleach for increasing exposure times. Initial and residual prion seeding activity following inactivation were measured using Real-Time Quaking Induced Conversion. In addition, we tested how passage of human sCJD into either transgenic mice that expressed human prion protein, or transmission of CJD to human cerebral organoids (CO), two common laboratory practices, may affect CJD prions' susceptibility to bleach inactivation. Our results show that bleach is effective against human sourced sCJD prions, and both treatment time and concentration of bleach were important factors for CJD inactivation. CJD derived from human brains, transgenic mouse brains or CO were all susceptible to inactivation with as low as a 10 percent bleach solution with a 30-minute exposure time or a 50 percent bleach solution with as little as a 1-minute exposure time.
朊病毒病是由错误折叠的、与疾病相关的朊病毒蛋白(PrPd)积累引起的可传播的致命哺乳动物神经系统疾病。克雅氏病(CJD)是最常见的人类朊病毒病,可通过散发性发病(sCJD)(~85%的 CJD 病例)、朊病毒蛋白基因的遗传突变(10-15%)或医源性传播(罕见)发生。PrPd 难以失活,许多降低朊病毒感染力的方法都很危险、腐蚀性强、昂贵或不切实际。确定用于消毒暴露于 CJD 的材料的可行且安全的方法对于医疗设施和研究机构至关重要。先前的研究表明,浓缩次氯酸钠(漂白剂)可有效灭活源自小鼠或豚鼠大脑的 CJD 朊病毒。不幸的是,适应啮齿动物的人类朊病毒可能与人类的折叠方式不同,并且适应啮齿动物的朊病毒可能与真正的 CJD 朊病毒具有不同的抗性或易感性。为了确认漂白剂对源自人类的 CJD 朊病毒有效,我们将不同亚型的 sCJD 感染的人脑匀浆暴露于不同浓度的漂白剂中,以增加暴露时间。使用实时晃动诱导转化测量失活后初始和残留朊病毒接种活性。此外,我们还测试了将人类 sCJD 传入表达人类朊病毒蛋白的转基因小鼠,或将 CJD 传播到人类脑类器官(CO)中,这两种常见的实验室操作如何影响 CJD 朊病毒对漂白剂失活的敏感性。我们的结果表明,漂白剂对源自人类的 sCJD 朊病毒有效,并且处理时间和漂白剂浓度都是 CJD 失活的重要因素。源自人脑、转基因小鼠脑或 CO 的 CJD 均易受失活影响,低至 10%的漂白剂溶液,暴露时间 30 分钟,或低至 50%的漂白剂溶液,暴露时间 1 分钟。