Applying genetic technologies to combat infectious diseases in aquaculture

Abstract

Disease and parasitism cause major welfare, environmental and economic concerns for global aquaculture. In this review, we examine the status and potential of technologies that exploit genetic variation in host resistance to tackle this problem. We argue that there is an urgent need to improve understanding of the genetic mechanisms involved, leading to the development of tools that can be applied to boost host resistance and reduce the disease burden. We draw on two pressing global disease problems as case studies-sea lice infestations in salmonids and white spot syndrome in shrimp. We review how the latest genetic technologies can be capitalised upon to determine the mechanisms underlying inter- and intra-species variation in pathogen/parasite resistance, and how the derived knowledge could be applied to boost disease resistance using selective breeding, gene editing and/or with targeted feed treatments and vaccines. Gene editing brings novel opportunities, but also implementation and dissemination challenges, and necessitates new protocols to integrate the technology into aquaculture breeding programmes. There is also an ongoing need to minimise risks of disease agents evolving to overcome genetic improvements to host resistance, and insights from epidemiological and evolutionary models of pathogen infestation in wild and cultured host populations are explored. Ethical issues around the different approaches for achieving genetic resistance are discussed. Application of genetic technologies and approaches has potential to improve fundamental knowledge of mechanisms affecting genetic resistance and provide effective pathways for implementation that could lead to more resistant aquaculture stocks, transforming global aquaculture.

Keywords: gene editing; genomic selection; host resistance; sea lice; transcriptomics; white‐spot syndrome virus.

FIGURE 1

Exploring the genetic basis of mechanisms providing host resistance. Host resistance to sea lice is likely affected by environmental and dietary factors that enhance or suppress salmon immunity, the immune cellular response (adaptive and innate immune systems), kairomones that attract the lice to the host and proteins that are secreted by the louse and suppress or trigger host immunity (red text). More detailed processes and factors likely to promote host immunity in coho, pink and more resistant strains of Atlantic salmon are listed in green text. To search for genes in the host that are up‐ or down‐regulated at key time points post‐infection: (1) genome‐wide association studies can identify genes mapping to chromosomal regions associated with host resistance, (2) single nuclei RNAseq (snRNAseq) can be used to study which populations of cell types are responding in host tissue close to the interface between the salmon and the louse, (3) spatial transcriptomics and spatial proteomics can be used to map precisely where the response occurs, (4) proteomics can be used to discover interactions between host cell and lice immunomodulatory proteins (suppressing or triggering host immunity), (5) RNAseq can be used to study semiochemical production by the host and transcriptomic response of the louse in response to kairomones, and, (6) gene editing can be used to test putative genes affecting host resistance, by experimentally challenging edited and non‐edited salmon with sea lice and comparing counts of attached lice

FIGURE 2

Simplified diagrammatic representation of the proposed immune response to white spot syndrome virus (WSSV) in shrimp. WSSV enters the cell using endocytic routes and induces both humoral and cellular responses from the host. Toll and immune deficiency (IMD) pathways are activated and dorsal and relsh are translocated to the nucleus inducing the expression of antimicrobial peptides that limit viral replication. C‐type lectin proteins can neutralise WSSV by binding to envelope proteins. Interestingly, WSSV is able to hijack the humoral pathways in order to facilitate its replication

FIGURE 3

Summary of metabolic effects during early (6–12 h) white spot syndrome virus (WSSV) infection. WSSV triggers aerobic glycolysis (Warburg effect) via activation of the PI3K‐Akt‐ mTOR pathway. The hallmark of aerobic glycolysis is the high levels of glucose consumption and lactate production. However other metabolic pathways are also enhanced, including the pentose phosphate pathway (PPP), the lipid metabolism pathway and the glutamine metabolism pathways. These metabolic changes support the high energy requirements of viral replication