Collaborative Research: The Emerging VHS Fish Virus - Gene Diversity Related to Cellular Immune Response Regulation

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，影响着全球的运动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在大湖地区的演变是如何促成其致病能力的，并应有助于对未来疫情的知情预测。因此，这些调查将把VHSv进化的研究与病毒破坏受感染鱼类免疫系统、导致疾病或死亡的途径结合起来。这些结果将有助于确定病毒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，从而将为了解病毒遗传变化（即病毒进化）与宿主反应之间的联系提供关键数据。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五大湖地区VHSv的传播，但这些研究将适用于其他病毒（鱼和其他病毒）。pi将为博物馆展品设计一个吸引人的移动显示器，并在会议和公共会议上更广泛地分发，以协助在科学界之外传播信息，并将培训研究生和本科生作为该项目的一部分。该项目的每一项目标都解决了关于这种疾病在大湖地区传播的一个具体问题。利用新的和现有的样品，利用菌株和亚菌株中的每个蛋白质基因（nv、N、M、L和P），评估VHSv基因的进化多样化模式和速率。结果将确定这些与新暴发分类群和地区的病毒选择如何相关，以及毒株是否以及如何成为地方性或流行病。通过比较VHSv毒株中的VHSv M和P（以及其他）基因功能，将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。综上所述，这些结果将对目前对一种新出现和具有挑战性的传染病的理解有价值。

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.