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

新的传染病的出现可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种宿主物种的病原体感染另一种新的宿主物种，然后进化出在宿主内良好复制和在宿主之间良好传播的能力时产生的。当病原体传播得足够好，可以无限期地留在新的宿主物种中时，这被称为疾病突发事件。这种现象也被称为“主机跳变”。预防宿主跳跃主要取决于确定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，对促进或阻止宿主跳跃的因素的了解是有限的。这项研究旨在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。研究人员还将广泛传播从这项工作中获得的知识给公众。病原体可根据溢出潜力进行分类。SP1病原体无法感染新的宿主。SP2型病原体可以感染新宿主但不传播。SP3型病原体可以感染新的宿主并传播，但不足以持续存在。在适当的环境下，这三种类型中的任何一种病原体都可能进化成已确立的病原体。目前的理论假设SP3的出现风险最高，其次是SP2，然后是SP1病原体。尽管有这些理论预测，但很少有实证工作探讨溢出风险如何随类别而变化。本研究将采用实验和理论相结合的方法来挑战这一理论。它将利用一种新的实验系统（秀丽隐杆线虫和秀丽隐杆线虫的原生宿主和病毒）确定解释突现成功变异的潜在机制。隐杆线虫-病毒系统允许病原体在大量复制宿主群体中传播。此外，初步数据显示，宿主-病毒组合跨越SP1、SP2和SP3病原体的范围。具体而言，该研究将首先表征隐杆线虫宿主暴露于其非原生病毒后的病毒动力学。其次，这项工作将描述隐杆线虫宿主暴露于其非本地病毒后病原体的进化。最后，这项工作将建立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（进化过程集群）和综合生物系统学部（共生、感染和免疫项目）联合资助。该奖项反映了美国国家科学基金会的法定使命，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。

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.