Using Caenorhabditis viruses to identify the ecological role of spillover outcome on the evolution of disease emergence

利用秀丽隐杆线虫病毒来确定溢出结果对疾病出现演变的生态作用

• 批准号: 2211322
• 负责人: David Kennedy
• 金额: $ 71.47万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2211322&HistoricalAwards=false
• 关键词: Using; Caenorhabditis; viruses; identify; ecological

The emergence of new infectious diseases can have important consequences for the health of many organisms. Most emerging diseases arise when a pathogen of one host species infects a new host species and then evolves the ability to replicate well within hosts and transmit well between hosts. When the pathogen transmits itself well enough to remain in the new host species indefinitely, this is referred to as a disease emergence event. This phenomenon is also known as a "host jump". Preventing host jumps depends critically on identifying traits associated with disease emergence so that actions can be taken early to stop the spread of the disease. However, knowledge of the factors that facilitate or prevent host jumps is limited. This research seeks to identify the conditions following exposure that determine risk of emergence. The findings of this research will have direct relevance for conservation efforts, food security and human health. The researcher will also widely disseminate the knowledge gained from this work to the public.Pathogens can be classified by spillover potential. SP1 pathogens are incapable of infecting new hosts. SP2 pathogens can infect new hosts but not transmit. SP3 pathogens can infect new hosts and transmit but not well enough to persist. Pathogens in any of these three categories could presumably, under the right circumstances, evolve to become established pathogens. Current theory assumes that emergence risk is highest for SP3, followed by SP2, followed by SP1 pathogens. Despite these theoretical predictions, little empirical work has explored how emergence risk varies by spillover class. This research will use experimental and theoretical approaches to challenge this theory. It will identify the underlying mechanisms that explain variation in emergence success using a novel experimental system (Caenorhabditis hosts and viruses native to C. elegans and C. briggsae). The Caenorhabditis-virus system allows for pathogen transmission in large, replicate host populations. Furthermore, preliminary data has shown that host-virus combinations span the range of SP1, SP2, and SP3 pathogens. Specifically, the research will first characterize virus dynamics following exposure of Caenorhabditis hosts to their non-native viruses. Second, the work will characterize the evolution of pathogens following exposure of Caenorhabditis hosts to their non-native viruses. Finally, the work will develop mathematical models connecting virus dynamics to host jump success.This project is jointly funded by the Division of Environmental Biology (Evolutionary Processes Cluster) and the Division of Integrative Organismal Systems (Symbiosis, Infection and Immunity Program).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.

新的传染病的出现可能会对许多生物体的健康产生重要后果。大多数新出现的疾病是当一个宿主物种的病原体感染一个新的宿主物种，然后进化出在宿主内良好复制并在宿主之间良好传播的能力时发生的。当病原体传播得足够好，足以无限期地留在新的寄主物种中时，这被称为疾病出现事件。这种现象也被称为“宿主跳跃”。防止宿主跳跃关键取决于识别与疾病出现相关的特征，以便及早采取行动阻止疾病的传播。然而，对促进或防止主机跳跃的因素的了解是有限的。这项研究试图确定暴露后决定出现风险的条件。这项研究的结果将与保护工作、粮食安全和人类健康直接相关。研究人员还将向公众广泛传播从这项工作中获得的知识。病原体可以根据溢出潜力进行分类。SP1病原体不能感染新寄主。SP2病原菌可以感染新寄主，但不能传播。SP3病原体可以感染新宿主并传播，但不足以持续存在。在适当的情况下，这三种病原体中的任何一种都可能进化为既定的病原体。目前的理论认为，SP3的出现风险最高，其次是SP2，其次是SP1病原体。尽管有这些理论预测，但很少有实证工作探索涌现风险如何因溢出类别而异。本研究将采用实验和理论相结合的方法来挑战这一理论。它将使用一种新的实验系统(线虫宿主和线虫和线虫本身的病毒)来确定解释羽化成功率差异的潜在机制。线虫-病毒系统允许病原体在大量复制的宿主群体中传播。此外，初步数据显示，宿主-病毒组合跨越了SP1、SP2和SP3病原体的范围。具体地说，这项研究将首先表征线虫宿主暴露于非本地病毒后的病毒动态。其次，这项工作将表征线虫宿主暴露于非本地病毒后病原体的进化。最后，这项工作将开发将病毒动力学与宿主跳跃成功联系起来的数学模型。该项目由环境生物学部门(进化过程集群)和综合组织系统部门(共生、感染和免疫计划)联合资助。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。