Collaborative Research: Gene Diversity of the VHS Fish Virus: Evolution of Cellular Immune Response and Pathogenesis

病毒性出血性败血症病毒（VHSV）是世界上最重要的鱼类疾病之一，影响到地球仪的体育捕鱼和商业捕鱼企业。VHSV最近才在五大湖出现，人们对它是如何到达的以及为什么它会周期性地导致大规模鱼类死亡知之甚少。拟议的项目将研究VHSV在大湖地区的演变如何促进其致病能力，并应有助于对未来疫情的预测。因此，调查将把对VHSV进化的研究与确定病毒破坏受感染鱼类免疫系统的方式结合起来，导致疾病或死亡。这些结果应该有助于确定病毒中的特定遗传变化如何导致对受感染鱼类的影响增强或减少，从而为理解病毒遗传变化之间的联系提供关键数据（即，病毒进化）和宿主的反应。研究结果将有助于更有效地预防、预测和控制VHSV，帮助国家和国际管理工作。虽然这项工作将侧重于VHSV在五大湖地区的传播，但这些研究将适用于其他病毒（鱼类和其他）。项目执行员将为博物馆展览设计一个吸引人的移动的展示，并在会议和公众集会上更广泛地分发，以协助向科学界以外的人传播信息，并将培训研究生和本科生，作为该项目的一部分，该项目的每一个目标都涉及一个关于这种疾病在五大湖地区传播的具体问题。将使用新的和现有的样本，使用菌株和亚株中的每种蛋白基因（N、N、M、L和P）评价VHSV基因的进化多样化模式和速率。结果将确定这些是如何与病毒选择在新的爆发类群和地区，以及是否和如何菌株成为地方性或流行性。将通过比较VHSv毒株之间的VHSv M和P（以及其他）基因功能，评估细胞和宿主反应，以确定抑制鱼类先天免疫反应的病毒基因内的突变如何影响功能。项目负责人将使用反向遗传学来评估M，P和L在调节先天免疫反应和病毒致病性中的作用。综合这些结果将是有价值的，在目前的理解一个新出现的和具有挑战性的传染病。

Viral Hemorrhagic Septicemia virus (VHSv) is one of the world's most important finfish diseases, impacting both sport fishing and commercial fishing ventures around the globe. VHSv emerged only recently in the Great Lakes, and little is known about how it arrived and why it periodically leads to large scale fish die-offs. The proposed project will examine how VHSv's evolution in the Great Lake region has contributed to its ability to cause disease, and should aid informed predictions about future outbreaks. Thus, the investigations will integrate studies on VHSv evolution with identification of the means by which the virus disrupts immune systems of infected fish, leading to sickness or death. These results should help to identify how specific genetic changes in the virus can lead to either enhanced or reduced impact on infected fish, and thus will provide critical data for understanding the connection between viral genetic changes (i.e., viral evolution) and the host's response. Results will contribute towards more effective prevention, prediction, and control of VHSv, aiding national and international management efforts. Although the work will focus on the spread of VHSv within the Great Lakes region, the studies will have application to other viruses (fish and otherwise). The PIs will design an attractive mobile display for museum exhibits and broader distribution at conferences and public meetings to assist in disseminating the information beyond the scientific community, and will train both graduate and undergraduate students as part of this project.Each of the aims of the project addresses a specific question about the spread of this disease in the Great Lakes region. Evolutionary diversification patterns and rates of VHSv genes will be evaluated using each protein gene (nv, N, M, L, and P) in strains and substrains, using new and existing samples. Results will determine how these are related to viral selection in new outbreak taxa and areas, and whether and how strains become endemic or epidemic. Cellular and host responses will be assessed to determine how mutations within viral genes that repress fish innate immune responses affect function by comparing VHSv M and P (and other) gene functions among VHSv strains. The project leaders will use reverse genetics to assess the role of M, P and L in modulating innate immune responses and viral pathogenicity. Taken together these results will be valuable in the present understanding of a new emerging and challenging infectious disease.