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次氯酸作为高危型 HPV 的消毒剂:作用机制的深入了解。

Hypochlorous acid as a disinfectant for high-risk HPV: Insight into the mechanism of action.

机构信息

Department of Physical Sciences, University of Washington Bothell, WA, USA.

Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

出版信息

J Med Virol. 2022 Jul;94(7):3386-3393. doi: 10.1002/jmv.27716. Epub 2022 Mar 23.

DOI:10.1002/jmv.27716
PMID:35277984
Abstract

Medical instruments that are not autoclavable but may become contaminated with high-risk human papillomaviruses (HPVs) during use must be thoroughly disinfected to avoid the possibility of iatrogenic transmission of infection. There is an expectation that prolonged soaking of instruments in the United States Food and Drug Administration-cleared chemical disinfectant solutions will result in high-level decontamination, but HPV16 and HPV18 are known to be resistant to commonly used formulations. However, they are susceptible to a variety of oxidative agents, including those based on chlorine. Here, we tested the efficacy of homogeneous hypochlorous acid (HOCl) solutions against mature infectious virions of HPV16 and HPV18 dried onto butadiene styrene coupons and ultrasonic probes. Both viruses were inactivated to >4 log reduction value (LRV) after 15 s on coupons and 5 min on ultrasonic probes. Morphologic changes became evident within those contact times by transmission electron microscopy when HPV16 virus-like particles were exposed to HOCl under identical conditions. Mass spectrometry analysis of trypsin-digested products of L1 capsid proteins exposed to HOCl showed that mostly conserved residues were modified by oxidation and that these changes rapidly lead to instability of the protein demonstrable on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Modifications to these residues may contribute to rapid virus inactivation. The use of homogeneous HOCl solutions for HPV decontamination provides a highly effective means of assuring the safety of nonautoclavable medical instruments.

摘要

医疗器械如果不能进行高压蒸汽灭菌,但在使用过程中可能会被高风险的人乳头瘤病毒(HPV)污染,必须进行彻底消毒,以避免医源性感染传播的可能性。人们期望美国食品和药物管理局批准的化学消毒剂溶液长时间浸泡器械会导致高水平的去污,但已知 HPV16 和 HPV18 对常用配方具有耐药性。然而,它们易受多种氧化剂的影响,包括基于氯的氧化剂。在这里,我们测试了均相次氯酸(HOCl)溶液对干燥在丁二烯-苯乙烯共聚物小卡和超声探头的 HPV16 和 HPV18 成熟感染性病毒粒子的功效。两种病毒在小卡上 15 秒和在超声探头 5 分钟后均被灭活到 >4 对数减少值(LRV)。当 HPV16 病毒样颗粒在相同条件下暴露于 HOCl 时,通过透射电子显微镜在这些接触时间内,形态变化变得明显。用 HOCl 暴露的 L1 衣壳蛋白的胰蛋白酶消化产物的质谱分析表明,大多数保守残基被氧化修饰,这些变化迅速导致蛋白质不稳定,在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)上可明显观察到。这些残基的修饰可能有助于病毒的快速失活。使用均相 HOCl 溶液进行 HPV 去污提供了一种非常有效的方法,可以确保非高压蒸汽灭菌医疗器械的安全性。

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