Virulence Tradeoffs in a Vertebrate Virus

随着最近出现了许多严重的人类疾病（如西尼罗河、非典型肺炎、汉坦病毒），了解决定病原体进化为毒性还是良性的因素变得越来越重要。传统观点认为，病原体应该总是朝着与宿主良性共存的方向进化。然而，有大量证据表明，病原体有时会进化成严重的疾病，这表明在某些情况下，高毒力可能是有利的。这被称为毒性权衡。在这个项目中，鱼类病毒IHNV及其虹鳟鱼宿主将被用来探索毒力的进化。毒力不同的病毒株将在一种新的系统中进行测试，以量化在活的幼年鳟鱼感染期间的病毒适应性。结果将用于开发一个人口规模模型，该模型将确定预测导致毒性增加的因素。最后，将通过比较在不同环境中发生的病毒场毒株的毒力来检验模型预测。病原体毒力的进化已经成为一个主要的研究领域，许多理论模型已经开发调用毒力权衡。由于普遍缺乏实验数据，特别是在脊椎动物宿主-病原体系统中，这一领域的进展受到阻碍。在这个项目中，实验和理论方法的结合将提供关于毒性权衡的存在和性质的新信息，增强我们对兽医和人类疾病出现的重要性的理解。该项目还将培训研究生和本科生，包括来自科学领域代表性不足群体的个人。

With the recent emergence of many severe human diseases (e.g., West Nile, SARS, Hantavirus), it has become increasingly important to understand the factors that determine whether pathogens evolve to become virulent or benign. The conventional wisdom states that a pathogen should always evolve towards a benign coexistence with its host. However, there is substantial evidence that pathogens sometimes evolve to cause severe disease, suggesting that high virulence may be advantageous in some cases. This is referred to as virulence trade-offs. In this project the fish virus IHNV and its rainbow trout host will be used to explore the evolution of virulence. Virus strains that differ in virulence will be tested in a novel system for quantifying viral fitness during infection in living juvenile trout. Results will be used to develop a population-scale model that will identify factors predicted to lead to increased virulence. Finally, the model predictions will be tested by comparing virulence of virus field strains that occur in different environments.The evolution of pathogen virulence has become a major field of investigation and numerous theoretical models have been developed invoking virulence trade-offs. Progress in this field is hampered by a general lack of experimental data, particularly in vertebrate host-pathogen systems. In this project a combination of experimental and theoretical approaches will provide novel information on the existence and nature of virulence tradeoffs, enhancing our understanding of how important veterinary and human diseases emerge. The project will also train graduate and undergraduate students, including individuals from groups under-represented in the sciences.