EAGER: Infectious Norovirus Persistence in Water

诺如病毒被认为是大多数因暴露于污水污染的水而引起的感染的原因。评估诺如病毒造成的风险需要能够准确测量和在水中培养它们。不幸的是，目前我们还不能在实验室中容易地培养诺如病毒。我们还缺乏合适的分子探针来快速准确地测量诺如病毒。最近的研究使用人类肠类（HIE）显示出作为一种技术，使准确培养诺如病毒的前景。该项目的目标是开发HIE作为表征传染性诺如病毒在水中持久性的工具。实现这一目标将需要评估HIE技术和其他工具之间的一致性，以评估该方法的准确性。这项工作的成功完成将使HIE方法能够作为诺如病毒的快速准确测量工具。拟议的项目将通过改善诺如病毒监测和控制工作，保护水，食品和娱乐中的人类健康，对社会和教育产生重大效益。除了这些社会效益，拟议的项目将有助于培训一名环境工程博士生在先进的诺如病毒培养方法。诺如病毒是一种重要的水传播病原体，可能占大多数感染所造成的暴露于污水污染的水。由于缺乏合适的分子或替代方法以及无法在实验室培养诺如病毒，测量诺如病毒在水中的持久性和灭活变得复杂。我们建议通过开发一种新的培养方法来解决这个问题，使用人类肠类（HIE）。这种方法是基于有希望的结果，显示出HIE能够实现诺如病毒的可再现培养。该工具将用于表征感染性诺如病毒在水中的持久性，并将结果与培养、分子和替代措施进行比较，以进行验证。诺如病毒在HIE中的培养仍然是高度专业化的。因此，这种方法的成功验证代表了理解传染性诺如病毒在水中持久性的潜在变革性进展。这也将使未来的调查传染性诺如病毒的命运在其他环境基质。这些进展将给社会带来广泛的惠益，特别是在饮用水、空气、粮食、农业和娱乐用水管理等领域。该项目将对社会和教育产生重大影响。准确测量和预测诺如病毒可以使我们能够积极应对疫情，减少疾病负担。除了技术成果外，该项目还将为培养一名环境工程博士生提供最先进的诺如病毒培养方法，研究成果将通过期刊出版物和会议报告广泛传播。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Norovirus is considered to be responsible for most infections resulting from exposure to sewage contaminated water. Assessing risk posed by norovirus requires the ability to accurately measure and cultivate them in water. Unfortunately, at present we cannot readily culture norovirus in the lab. We also lack suitable molecular probes to rapidly and accurately measure norovirus. Recent studies using human intestinal enteroids (HIE) have shown promise as a technique to enable accurate cultivation of norovirus. The goal of this project is to develop HIE as a tool to characterize infectious norovirus persistence in water. Achieving this goal will require evaluating the agreement between the HIE technique and other tools to assess the accuracy of the method. Successful completion of this work will enable the use of HIE methods as a rapid and accurate measurement tool for norovirus. The proposed project will have significant benefits to society and education through improved norovirus monitoring and control efforts to protect human health in water, food, and recreation. In addition to these societal benefits, the proposed project will contribute to the training of an environmental engineering PhD student in cutting-edge norovirus cultivation approaches.Norovirus is an important waterborne pathogen that likely accounts for the majority of infections resulting from exposure to sewage contaminated water. Measuring norovirus persistence and inactivation in water is complicated by a lack of suitable molecular or surrogate methods and an inability to culture norovirus the laboratory. We propose to address this limitation by developing a novel cultivation approach using human intestinal enteroids (HIE). This approach is based on promising results showing HIEs have enabled reproducible cultivation of norovirus. This tool will be used to characterize infectious norovirus persistence in water and results compared to culture, molecular, and surrogate measures for validation. Cultivation of norovirus in HIE remains highly specialized. Thus, successful validation of this approach represents a potentially transformative advance in understanding infectious norovirus persistence in water. It would also enable future investigations of infectious norovirus fate in other environmental matrices. Such advances would have broad benefits to society, particularly in the fields of drinking water, air, food, agriculture, and recreational water management. The proposed project will have significant benefits to society and education. Accurate measurement and forecasting of norovirus may allow us to proactively respond to outbreaks, reducing the disease burden. In addition to technical results, the proposed project will contribute to the training of an environmental engineering PhD student in cutting-edge norovirus cultivation approaches and research results will be disseminated widely via journal publications and a conference presentation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.