Virulence Evolution After Viral Host Jump and Emergence

随着时间的推移，新出现的病原体对宿主的危害是增加还是减少，这是预测疾病爆发严重程度的关键。当新的传染病出现时，对人类、农业和野生动物的影响有时是毁灭性的，例如埃博拉病毒、禽流感和西尼罗河病毒。然而，其他突发疾病的严重程度要小得多，甚至可能被忽视。预测突发病原体将造成的危害程度（即毒力）的能力是有限的。该项目将通过确定影响新宿主物种感染后毒力变化的因素，提高我们预测新发疾病严重程度的能力。大量的工作试图解决这个问题。几乎所有这些工作都有相同的缺点，即从宿主-病原体相互作用开始就没有关键数据。宿主跳跃标志着宿主-病原体相互作用的开始，因此它们为研究毒力进化的整个轨迹提供了唯一的机会。虹鳟鱼和鲑鱼中的鱼类病毒IHNV（感染性造血坏死病毒）是为数不多的系统之一，可以从两个独立的宿主跳跃开始观察这些变化，使其成为理想的研究模型。从这些宿主跳跃的研究中获得的见解将告知如何最好地分配资源，以应对新出现的疾病对公共卫生、经济和生物多样性的影响。该项目还将涉及通过教育和培训研究生、本科生和技术人员来建设管理传染病的能力，重点是代表性不足的群体。病原体在新宿主中出现后，其毒力是向上进化还是向下进化，是进化生态学和传染病管理的一个基础问题。适合此类研究的系统很少，因为它们需要1)在宿主跳跃之前和之后广泛收集病原体分离样本，这些样本跨越足够的时间以发生进化，2)生态相关的祖先和新宿主进行普通的花园实验，以及3)在这些实验中测量毒力和关键适应性成分（如传播潜力）的能力。IHNV病毒是少数满足这些要求的病原体之一。自20世纪50年代以来，IHNV在太平洋西北地区的许多鲑鱼种群中都是地方性和流行病，并使两个独立的宿主跳跃到虹鳟鱼中。本研究将利用涵盖两次宿主跳跃事件和随后50年的3000株IHNV分离株，开展四个研究重点。(1)实验确定病毒在羽化过程中的毒力(2)实验确定病毒在羽化过程中的传播潜力。(3)全基因组测序以确定毒力和传播潜力的遗传相关性。(4)建立数学模型，剖析驱动毒力进化的选择力，评估环境变化的进化风险。这项研究有望表明，毒力、传播潜力和生态环境之间的相互作用可以用来解释新出现的病原体的毒力随时间的变化。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。

Whether a newly emerged pathogen will become more or less harmful to its host over time is key to predicting the severity of disease outbreaks. When new infectious diseases emerge, the effects on humans, agriculture and wildlife are sometimes devastating, as exemplified by Ebola, avian influenza, and West Nile virus. However, other emergent diseases are much less severe, and may even go unnoticed. The ability to predict the level of harm (i.e. virulence) that an emergent pathogen will cause is limited. This project will improve our ability to predict the severity of emerging diseases by identifying the factors that influence changes in virulence after the infection of a new host species. An extensive body of work has attempted to address this question. Almost all this work has the same shortcoming, key data are not available from the very start of the host-pathogen interaction. Host jumps mark the beginning of a host-pathogen interaction and they therefore provide the only opportunity to study entire trajectories of virulence evolution. The fish virus IHNV (infectious hematopoietic necrosis virus) in rainbow trout and salmon is one of the few systems where samples are available to look at these changes from the beginning for two, independent host jumps, making it an ideal research model. Insights from the study of these host jumps will inform how best to allocate resources to combat the public health, economic, and biodiversity impacts of emerging diseases. The project will also involve building capacity for the management of infectious disease through the education and training of graduate students, undergraduates, and technicians, with a focus on under-represented groups. Whether the virulence of a pathogen will evolve upwards or downward after emergence in a new host, is a foundational question in evolutionary ecology and infectious disease management. Suitable systems for such studies are rare because they require 1) an extensive collection of pathogen isolates sampled before and after host jumps, which span enough time for evolution to occur, 2) ecologically relevant ancestral and new hosts in which to do common garden experiments, and 3) the ability to measure virulence and key fitness components such as transmission potential in these experiments. The virus IHNV is one of the few pathogens that meet these requirements. IHNV has been both endemic and epidemic in many salmonid fish populations of the Pacific Northwest since the 1950s, and made two independent host jumps into rainbow trout. This research will utilize a collection of 3000 IHNV isolates that covers the two host jump events and five subsequent decades to pursue four research foci. (1) Experimental determination of viral virulence throughout emergence (2) Experimental determination of viral transmission potential throughout emergence. (3) Whole genome sequencing to determine genetic correlates of virulence and transmission potential. (4) Mathematical modeling to dissect the selective forces driving virulence evolution and assess the evolutionary risks of environmental change. The research is expected to show that interactions between virulence, transmission potential, and the ecological setting can be used to explain changes in the virulence of an emerging pathogen over time.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.