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: 10373373
• 负责人: Yun Shen
• 金额: $ 22.47万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373373
• 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; design; dosage; emerging pathogen; extracellular vesicles; food sanitation; operation; particle; pathogen; prevent; 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.

项目摘要/摘要 轮状病毒和诺如病毒是众所周知的，可导致人类严重的肠胃炎和出色的公共卫生 关注。两种病毒在环境上都是持续存在的，可以通过直接接触 受感染的人或污染的表面以及受污染的水和食物。消毒会使这些失活 持续的病毒并防止感染暴发。几乎所有以前的研究都考虑轮状病毒和 诺如病毒作为个体，在生物医学研究中的自由病毒颗粒，直到最近的发现表明 轮状病毒和诺如病毒可以在体外作为病毒簇在具有丰富脂质的细胞外蔬菜内传播 膜结构，即囊泡粘的病毒簇（为简单起见病毒蔬菜）。囊泡粘的轮状病毒 诺如病毒簇是重要的新兴病原体，因为它们是环境稳定的，广泛的 现在，比其自由病毒颗粒对应物更具感染力；但是，他们当前失活 消毒策略尚不清楚。而且，消毒机制在很大程度上不清楚，这阻止了我们 从有效，健壮，广谱和低成本消毒过程的合理设计。这个项目寻求 评估传统消毒策略的性能，以灭活囊泡的轮状病毒和 诺如病毒簇，阐明病毒囊泡失活的机制，并产生新的消毒 有效病毒囊泡灭活的过程。我们的中心假设是囊泡粘的病毒簇 与自由病毒的对应物相比，消毒和消毒更加持久，并损害了消毒 病毒蔬菜中的多种生物成分更有效。具体目标1将评估 传统的消毒剂，即漂白剂，紫外线（单色UV 254） NM），一种表面活性剂（氯化铵），乙醇及其组合。剂量 消毒剂及其在消毒中的性能将确定产生剂量反应关系， 将与自由病毒进行比较。特定的目标2将阐明失活的机制 传统的消毒剂通过传统的消毒剂捕获的病毒簇，以了解决定的关键因素 消毒性能。病毒蔬菜的生物成分损害以及对病毒蔬菜的影响 消毒后宿主细胞中的生命周期将进行评估。特定目标3将评估新兴的消毒剂， 即，多色紫外线辐照和活化的过硫酸盐，用于灭活蔬菜裂片的病毒簇。两个都 将探索消毒性能和机制。我们的研究将阐明优化的需求 当前的消毒范式并为轮状病毒和诺如病毒制定新的消毒策略，并且 更广泛的健康影响，因为研究结果可以转化为其他相关病毒的失活 （例如，脊髓灰质炎病毒，coxsacchivievivirus，鼻病毒，丙型肝炎和E病毒），它们在环境上持续存在， 还可以形成蔬菜粘液的病毒簇。