EAGER: Infectious Norovirus Persistence in Water

诺沃克病毒被认为是接触污水污染水造成的大多数感染的罪魁祸首。评估诺沃克病毒构成的风险需要准确测量并在水中培养它们的能力。不幸的是，目前我们还不能在实验室中容易地培养诺沃克病毒。我们也缺乏合适的分子探针来快速准确地检测诺沃克病毒。最近使用人类肠类肠道(HIE)的研究表明，这是一种能够准确培养诺沃克病毒的技术。该项目的目标是开发HIE作为表征水中传染性诺沃克病毒持久性的工具。实现这一目标将需要评估HIE技术与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方法能够作为诺沃克病毒的快速和准确的测量工具。拟议的项目将通过改进诺沃克病毒监测和控制工作，在水、食品和娱乐方面保护人类健康，从而对社会和教育产生重大好处。除了这些社会效益外，拟议的项目还将有助于培训一名环境工程学博士生，掌握尖端的诺沃克病毒培养方法。诺沃克病毒是一种重要的水媒病原体，可能是接触污水污染的水引起的大部分感染的原因。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沃克病毒，因此测量诺沃克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使用人类肠样(HIE)的新的培养方法来解决这一限制。这种方法的基础是有希望的结果表明，HIE已经使诺沃克病毒的可复制培养成为可能。该工具将用于表征传染性诺沃克病毒在水中的持久性，并与培养、分子和替代措施进行比较，以进行验证。在缺氧缺血性脑病中培养诺沃克病毒仍然高度专业化。因此，这一方法的成功验证代表着在理解传染性诺沃克病毒在水中的持久性方面取得了潜在的变革性进展。这也将使未来能够研究传染性诺沃克病毒在其他环境基质中的命运。这些进展将给社会带来广泛的好处，特别是在饮用水、空气、食品、农业和娱乐用水管理领域。拟议中的项目将对社会和教育产生重大好处。对诺沃克病毒的准确测量和预测可能使我们能够主动应对疫情，从而减轻疾病负担。除了技术成果，拟议的项目还将有助于培训一名环境工程学博士生掌握尖端的诺沃克病毒培养方法，研究成果将通过期刊出版物和会议演示文稿广泛传播。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.