Vesicle-Cloaked Virus Clusters as Emerging Pathogens: Will They Challenge Current Disinfection Paradigm?

囊泡包裹的病毒簇作为新兴病原体：它们会挑战当前的消毒范式吗？

• 批准号: 10494266
• 负责人: Yun Shen
• 金额: $ 26.49万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10494266
• 关键词: Adopted; Antiviral Agents; Attention; Benchmarking; Binding; Biological; Biomedical Research; Capsid; Cations; Cell Culture Techniques; Cells; Cessation of life; Chlorides; Communicable Diseases; Coronavirus; Coxsackie Viruses; Developing Countries; Diarrhea; Disease Outbreaks; Disinfectants; Disinfection; Dose; Ethanol; Feces; Food; Gastroenteritis; Genome; Harvest; Health; Hepatitis A; Hepatitis E virus; Hospital Costs; Human; Human poliovirus; Hygiene; In Vitro; Individual; Infection; Infection prevention; International; Interruption; Kinetics; Lead; Light; Lipids; Medical Care Costs; Membrane; Membrane Lipids; Murine hepatitis virus; Mus; Norovirus; Outcomes Research; Oxides; Performance; Persons; Process; Proteins; Public Health; Reaction; Rhinovirus; Rotavirus; Surface; Translating; Ultraviolet Rays; Vaccination; Vaccines; Vesicle; Viral; Virus; Water; Work; cost; dosage; emerging pathogen; extracellular vesicles; food sanitation; operation; particle; pathogen; prevent; rational design; response; surfactant; transmission process; ultraviolet irradiation; virus envelope

Project Summary/Abstract Rotavirus and norovirus are well-known to lead to serious gastroenteritis in humans and great public health concerns. Both viruses are environmentally persistent, and they can be transmitted via direct contact with an infected person or contaminated surfaces, as well as polluted water and food. Disinfection can inactivate these persistent viruses and prevent infectious disease outbreaks. Almost all previous studies consider rotavirus and norovirus as individual, free viral particles in biomedical research, until a recent finding demonstrated that rotavirus and norovirus could transmit in vitro as viral clusters inside extracellular vesicles that have a lipid-rich membrane structure, i.e., vesicle-cloaked virus clusters (viral vesicles for simplicity). Vesicle-cloaked rotavirus and norovirus clusters are important emerging pathogens, because they are environmentally stable, widely present, and more infectious than their free viral particle counterpart; however, their inactivation by current disinfection strategies is unknown. Moreover, disinfection mechanisms are largely unclear, which prevents us from rational design of effective, robust, broad-spectrum, and low-cost disinfection processes. This project seeks to evaluate the performance of conventional disinfection strategies for inactivating vesicle-cloaked rotavirus and norovirus clusters, elucidate the mechanisms of viral vesicle inactivation, and develop new disinfection processes for effective viral vesicle inactivation. Our central hypothesis is that the vesicle-cloaked virus clusters are more persistent in disinfection compared to their counterpart of free viruses, and disinfection that damages multiple biological components in viral vesicles is more effective. Specific Aim 1 will evaluate the inactivation of vesicle-cloaked virus clusters by conventional disinfectants, i.e., bleach, ultraviolet light (monochromatic UV 254 nm), a surfactant (didecyldimethylammonium chloride), ethanol, and their combination. The dosage of disinfectants and their performance in disinfection will be determined to generate a dose-response relationship, which will be compared with that for free viruses. Specific Aim 2 will elucidate the mechanisms of inactivating vesicle-cloaked virus clusters by conventional disinfectants to understand the key factor that determines disinfection performance. The damage of biological components of viral vesicles and the impact on viral vesicles’ lifecycle in the host cells after disinfection will be evaluated. Specific Aim 3 will evaluate emerging disinfectants, i.e., polychromatic UV irradiation and activated persulfate, for inactivating vesicle-cloaked virus clusters. Both disinfection performance and mechanisms will be explored. Our study will shed light on the need for optimizing current disinfection paradigm and developing new disinfection strategies for rotavirus and norovirus, and it has a broader health impact because research outcomes can be translated into inactivating other related viruses (e.g., poliovirus, coxsackievirus, rhinovirus, hepatitis A and E viruses), which are environmentally persistent and could also form vesicle-cloaked virus clusters.

项目概要/摘要 众所周知，轮状病毒和诺如病毒会导致人类严重胃肠炎并严重影响公共卫生 的担忧。这两种病毒都具有环境持久性，可以通过直接接触传播 感染者或受污染的表面，以及受污染的水和食物。消毒可以灭活这些物质 持久性病毒并防止传染病爆发。几乎所有先前的研究都考虑了轮状病毒和 诺如病毒在生物医学研究中作为单独的、游离的病毒颗粒，直到最近的一项发现表明 轮状病毒和诺如病毒可以作为富含脂质的细胞外囊泡内的病毒簇在体外传播 膜结构，即囊泡包裹的病毒簇（为简单起见，称为病毒囊泡）。囊泡包裹的轮状病毒 诺如病毒簇是重要的新兴病原体，因为它们环境稳定，广泛传播 存在，并且比其游离病毒颗粒对应物更具传染性；然而，它们通过电流失活 消毒策略尚不清楚。此外，消毒机制在很大程度上尚不清楚，这阻碍了我们 来自有效、稳健、广谱和低成本消毒工艺的合理设计。该项目寻求 评估灭活囊泡轮状病毒的常规消毒策略的性能和 诺如病毒簇，阐明病毒囊泡灭活机制，开发新的消毒方法 有效灭活病毒囊泡的过程。我们的中心假设是，囊泡包裹的病毒簇 与游离病毒相比，其消毒效果更持久，且消毒效果更佳 病毒囊泡中的多种生物成分更有效。具体目标 1 将评估失活 使用常规消毒剂（即漂白剂、紫外线（单色 UV 254 nm）、表面活性剂（二癸基二甲基氯化铵）、乙醇及其组合。剂量为 将确定消毒剂及其消毒性能以产生剂量反应关系， 这将与免费病毒进行比较。具体目标 2 将阐明失活机制 通过常规消毒剂观察囊泡包裹的病毒簇，了解决定的关键因素 消毒性能。病毒囊泡生物成分的损伤及其对病毒囊泡的影响 将评估消毒后宿主细胞的生命周期。具体目标 3 将评估新兴消毒剂， 即多色紫外线照射和活化的过硫酸盐，用于灭活囊泡隐藏的病毒簇。两个都 将探讨消毒性能和机制。我们的研究将揭示优化的必要性 现有的消毒模式并针对轮状病毒和诺如病毒开发新的消毒策略，并且已经 更广泛的健康影响，因为研究成果可以转化为灭活其他相关病毒 （例如脊髓灰质炎病毒、柯萨奇病毒、鼻病毒、甲型肝炎病毒和戊型肝炎病毒），这些病毒在环境中具有持久性和 也可以形成囊泡包裹的病毒簇。