New approaches to characterize viral diseases affecting Atlantic salmon

The Atlantic salmon aquaculture industry is worth >£1 billion to the UK economy per annum and represents an important provider of employment and food security. However the expansion of this industry is threatened by a range of infectious diseases, including several different viruses, which can cause fish mortality, slow growth and reduce the quality of the final flesh product, in addition to the substantial costs of treating fish stock with expensive vaccines and preventative measures. Thus the overall goal of this project is to build research capacity in UK (and global) aquaculture by developing tools to characterise genomic diversity in disease-causing salmonid viruses and use this genomic information to characterise the dispersal, adaptation and pathogenicity of these viruses. One untapped framework to support the expansion of the salmon aquaculture industry is the use of 'evolutionary epidemiology'. This field attempts to characterise the epidemiology of pathogens using quantitative phylogenetic methods which can lead to data on the origins, transmission and adaptation of viruses. Such approaches have already been used to provide insight into the human diseases caused by Ebola, HIV and influenza-A. However one of the current limitations of using this approach to benefit aquaculture is a lack of tools to effectively and efficiently sequence and analyse genome-scale variation between and within viral strains. Moreover, there is a current lack of detailed insights into how variation in salmonid viruses is ultimately linked to pathogenicity and prospects for disease severity, which might be resolved with a genome-wide investigation. To achieve this goal, our project will develop molecular and computational tools for research of diseases affecting salmonid aquaculture, focussing on the widely present salmonid alphavirus (SAV) and infectious salmon anaemia virus (ISAV). The specific objectives are: 1) To develop tools for viral genome sequencing, rapid diagnostics and analysis of viral diversity using current generation sequencing and bioinformatics tools for assembly and annotation. This approach will generate data by second and third generation sequencing platforms. This work will generate protocols that will be broadly used in the future for applied and fundamental fish virus research. 2) To develop phylogenetic approaches to model viral population dynamics - inferring viral origins, dispersal, transmission routes and population growth. This objective will use newly generated (i.e. under objective 1) and archived sequence data sampled from salmonid farms and the natural environment, including hundreds of salmonid individuals and wild species acting as potential disease reservoirs. This approach will generate new epidemiological insights about salmonid viruses affecting aquaculture. 3) To characterize viral adaptation in the natural environment and under in vitro conditions of cell culture through serial passaging. This approach will identify adaptive sequence variation associated with distinct disease outbreaks and host species, as well as that allowing adaptation to cell culture, which may alter a virus's scope to cause cytopathic effects in vitro and modify pathogenicity in vivo. This will therefore inform a better understanding of the functional-evolutionary basis of salmonid virus pathogenicity.