New approaches to characterize viral diseases affecting Atlantic salmon

Lead Research Organisation: University of Aberdeen
Department Name: Inst of Biological and Environmental Sci

Abstract

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 ad 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.

Publications

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publication icon
Gallagher MD (2018) Nanopore sequencing for rapid diagnostics of salmonid RNA viruses. in Scientific reports

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M010996/1 01/10/2015 30/09/2023
1804933 Studentship BB/M010996/1 01/10/2016 30/09/2020 Michael Gallagher
 
Description - An original objective of the project was to develop methods to routinely sequence the whole genomes of viruses affecting salmonids in aquaculture. This has been achieved using multiple methods (e.g. MinION sequencing, Illumina sequence capture).
- Viral strain diversity is far higher than previously thought in salmonid alphavirus infections
- Human-mediated transmission of virus dominates the spread of SAV between geographically distant farms
- Genome sequencing provides much better resolution of the evolution of SAV compared to current standards of sequencing an individual gene for genotyping
Exploitation Route Further research is required to determine if there is a link between viral diversity and disease phenotype. Additionally, with the knowledge of much greater genetic diversity, tracking viral transmissions will become more nuanced and will require much denser sampling of infected fish.
Sectors Agriculture, Food and Drink,Environment

 
Description MASTS Small Grants
Amount £3,000 (GBP)
Funding ID SG406 
Organisation Marine Alliance for Science and Technology for Scotland 
Sector Public
Country United Kingdom
Start 06/2017 
End 07/2017
 
Description Microbiology Society Conference Grant 2018
Amount £233 (GBP)
Funding ID GA000307 
Organisation Microbiology Society 
Sector Learned Society
Country Unknown
Start 02/2018 
End 04/2018
 
Description Novel sequencing approaches to characterize viral diseases in salmon aquaculture: an undergraduate research experience
Amount £1,500 (GBP)
Organisation Marine Alliance for Science and Technology for Scotland 
Sector Public
Country United Kingdom
Start 07/2017 
End 07/2017
 
Title Nanopore sequencing of aquaculture viruses 
Description Methods for targeted whole genome sequencing were developed for several economically important aquaculture RNA viruses for use on nanopore MinION sequencing platform. No whole genome sequencing of these viruses had previously been performed using nanopore sequencing. This work also established this method for use in other experimental scenarios and is currently being used for other projects. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? Yes  
Impact NA 
URL https://www.nature.com/articles/s41598-018-34464-x
 
Title Targeted sequence capture of viruses in aquacultured fish 
Description Using a wide-ranging panel of probes, tiled across the genomes of several important aquaculture-related RNA viruses, a whole genome sequencing approach was established to efficiently enrich for viral nucleic acids. This was validated using a number of viral isolates to detect and characterise multi-viral infections which can produce important industry-regulator information. This approach has allowed us to study viral genetic diversity using an unbiased method unlike any other previously attempted. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? No  
Impact Not applicable yet - the paper is currently in preparation 
 
Description Nanopore whole genome sequencing of a novel SAV subtype 
Organisation Marine Institute
Country Ireland 
Sector Public 
PI Contribution Whole genome sequencing of a salmonid alphavirus isolate representing a novel subtype was performed along with bioinformatic and phylogenetic analyses of the resulting genome sequence
Collaborator Contribution Provision of the viral isolate, PCR amplicons and downstream analyses of the sequence made by Dr Neil Ruane (sample provision) and Andy Tighe (lab work and data analysis)
Impact Research article manuscript in prep currently
Start Year 2018
 
Description Whole genome sequencing of SAV2 and SAV3 isolates on the MinION 
Organisation Zoetis
Country United States 
Sector Private 
PI Contribution MinION whole genome sequencing, bioinformatic analysis and phylogenetic analysis of several salmonid alphavirus isolates
Collaborator Contribution Viral RNA was provided by PHARMAQ-Analytiq (part of Zoetis), as well as intellectual contributions to the analyses
Impact Ongoing project but potential to inform governmental policy surrounding the spread of SAV within Norway
Start Year 2018
 
Description GCFR Zoonoses Workshop - Talk on rapid Nanopore sequencing of viral pathogens 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact I was an invited speaker at a GCRF Zoonoses workshop held at the University of Aberdeen and hosted by Dr Sandra Telfer. I spoke about my work on using Nanopore sequencing as a rapid and accurate alternative to other sequencing methods in the field. The primary audience were researchers and disease surveillance workers based in Madagascar (who Dr Telfer collaborates with) but also included researchers at the University of Aberdeen and collaborators from research institutes in England
Year(s) Of Engagement Activity 2017
 
Description Oral Presentation at PD Trination conference - Bergen March 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact I gave a presentation at the PD Trination conference in Bergen, Norway regarding rapid whole genome sequencing on the Nanopore platform of salmonid alphavirus - the viral agent of an economically important disease in salmon farming. The primary audience were members of Irish, Scottish and Norwegian aquaculture research institutes, leaders in the industry and Norwegian policy makers.
Year(s) Of Engagement Activity 2018
 
Description Presentation to industry collaborator - PHARMAQ - 29th May 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact I gave a presentation and Q&A session to industry leaders at PHARMAQ Analytiq (part of animal health company Zoetis). This was in direct relation to my work on Nanopore sequencing of RNA viruses which they wanted to explore as a method for disease surveillance in Norwegian aquaculture.
Year(s) Of Engagement Activity 2018
 
Description Seminar at the Infectious disease diagnosis symposium - 14th Nov 2018, University of Edinburgh. Talk "'Advanced sequencing diagnostics of salmon viral disease reveals unrecognized strain diversity affecting aquaculture" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact I gave a talk titled "Advanced sequencing diagnostics of salmon viral disease reveals unrecognized strain diversity affecting aquaculture'. The purpose was to outline the progress made in our understanding of fish virus genetic diversity at the whole genome level, gained from the BBSRC award in question (Mike Gallagher's PhD). The audience was diverse, ranging from medical practitioners working in diagnosics, to researchers working on improving animal production.
Year(s) Of Engagement Activity 2018
URL https://www.ed.ac.uk/vet/news-events/events/infectious-disease-diagnosis-symposium-programme
 
Description Seminar at the Roslin Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact I gave a seminar at the Roslin Institute, which was an overview of my PhD research to date. The seminar is weekly and is pitched at other members of the Roslin Institute but not necessarily experts in my field. I presented my work on rapid whole genome sequencing as well as characterising the genetic diversity found in natural viral infections in salmon farming.
Year(s) Of Engagement Activity 2019
 
Description Seminar at the Roslin Institute: "Farmed Fish Integrative Genomics" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact I gave a seminar at the Roslin Institute, which was an overarching overview of the major research projects in my lab. The seminar was linked to job vacancy, so pitched towards the relevance of my work to BBSRC/UKRI remit and the interests/remit of the Roslin Institute. I was succesful in getting the position (Reader, University of Edinburgh), so a major impact followed this seminar.
Year(s) Of Engagement Activity 2018