Genomic epidemiological determination of routes of pathogenic virus transmission between farmed salmon

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Viruses that cause disease and death in farmed salmon harm the UK's economy, increase the carbon and environmental footprint of production, and reduce fish welfare. Two viruses, called piscine myocarditis virus (PMCV) and infectious salmon anaemia virus (ISAV) are particularly damaging. For every eight salmon that die of known causes on fish farms, one death is caused by PMCV. ISAV is less commonly detected in the UK, and the UK is currently considered free of the disease. However, introductions of ISAV have been shown to nearly destroy entire salmon industries in other countries and therefore protecting against new outbreaks remains critical as the UK expands salmon production to meet growing global demand. Despite the severe problems caused by these viruses, we do not fully understand how they transmit between farms. Our lack of understanding of how viruses enter and persist on farms has prevented action that can improve disease control.We propose to use virus genomic sequencing and genomic analyses to determine the routes of ISAV and PMCV transmission, and how and where pathogenic lineages emerge. Many viruses evolve very rapidly, and acquire genetic changes as they transmit between hosts. Using the evolved patterns of virus genetic changes to reconstruct ancestral relationships between viruses can be used to track how they transmit. Generated virus genomes additionally provide important information on the genetic basis for disease severity, and how pathogenic strains emerge. This approach has been widely used in public health to understand disease in humans, but opportunities to study disease transmission in farmed fish are being missed. We will answer several key questions that will improve our understanding of how to eliminate transmission. Fish are moved between farms as they grow, from egg and progeny in tanks, to inland freshwater sites as juveniles, and finally to the sea at adulthood. Firstly, we will reconstruct transmission to determine whether each virus tends to transmit between farms at the same production stage, or between different stages. This would indicate where biosecurity improvements are best focused. Secondly, we will determine what characteristics of a farm make it more likely to become infected or transmit these viruses with other farms. Identified characteristics could be used to improve surveillance for viruses at certain points in the fish supply chain, leading to more rapid detection and control if viruses are present. Thirdly, we will determine whether wild fish are a source of infection of PMCV, or whether they only rarely become infected when they come into contact with infected farms. The distinction is important to determine whether wild fish can easily infect fish on farms, or whether in contrast wild fish must be better protected to prevent establishment of virus transmission within wild populations. Finally, we seek to understand how genetic changes in the virus lead to more or less severe disease. This could be used to improve genetic 'early warning systems' for risk of disease emergence in fish or improve vaccinations, and are more broadly useful to understand how related viruses evolve and cause disease in other species. The approaches that we use in this research will also be broadly applicable to viral diseases, improving our ability to rapidly respond to new viral outbreaks in humans and other animalsTogether, our results will contribute to reducing disease amongst farmed salmon. This will lead to improved fish welfare, a more sustainable industry, cheaper cost of fish to the consumer because of reduction in loss, and greater economic value of the industry. Our results will be valuable to the UK, where salmon is the second most valuable food export, but also to producers and consumers in other markets worldwide.