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Virulence Evolution After Viral Host Jump and Emergence

病毒宿主跳跃和出现后的毒力进化

基本信息

批准号：
1754692
负责人：
Andrew Wargo
金额：
$ 119.5万
依托单位：
College of William & Mary Virginia Institute of Marine Science
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1754692&HistoricalAwards=false
关键词：
Virulence Evolution After Viral Host

项目摘要

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.

新出现的病原体是否会随着时间的推移对其宿主造成更大或更小的伤害，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低得多，甚至可能被忽视。预测新出现的病原体将造成的危害水平（即毒力）的能力有限。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，提高我们预测新出现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，从宿主-病原体相互作用的一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，因此它们提供了研究毒力进化整个轨迹的唯一机会。虹鳟鱼和鲑鱼中的鱼类病毒IHNV（传染性造血细胞坏死病毒）是为数不多的系统之一，其中样品可用于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为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提供信息。该项目还将通过对研究生、本科生和技术人员的教育和培训，建设传染病管理能力，重点是代表性不足的群体。病原体在新宿主中出现后毒力是向上还是向下进化，是进化生态学和传染病管理中的一个基本问题。适用于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采样的病原体分离物的广泛收集，其跨越足够的时间以使进化发生，2）与生态相关的祖先和新宿主，以进行常见的花园实验，以及3）在这些实验中测量毒力和关键适应性组分（如传播潜力）的能力。IHNV病毒是符合这些要求的少数病原体之一。自20世纪50年代以来，IHNV在太平洋西北部的许多鲑鱼种群中既是地方性的又是流行性的，并在虹鳟鱼中进行了两次独立的宿主跳跃。这项研究将利用收集的3000 IHNV分离物，涵盖两个主机跳事件和随后的五个十年追求四个研究重点。(1)整个出苗过程中病毒毒力的实验测定（2）整个出苗过程中病毒传播潜力的实验测定。(3)全基因组测序，以确定毒力和传播潜力的遗传相关性。(4)数学建模，剖析驱动毒力进化的选择力，评估环境变化的进化风险。该研究预计将表明，毒力，传播潜力和生态环境之间的相互作用可以用来解释随着时间的推移，在一个新兴的病原体毒力的变化。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。