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.
