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Gene expression analyses in Atlantic salmon challenged with infectious salmon anemia virus reveal differences between individuals with early, intermediate and late mortality.

ABSTRACT: BACKGROUND: Infectious salmon anemia virus (ISAV) causes a multisystemic disease responsible for severe losses in salmon aquaculture. Better understanding of factors that explain variations in resistance between individuals and families is essential for development of strategies for disease control. To approach this, we compared global gene expression using microarrays in fish dying early and late in the time course following infection from a highly pathogenic ISAV. RESULTS: Tissues (gill, heart, liver and spleen) from infected Atlantic salmon (cohabitation, ISAV Glesvaer 2/90 isolate) were collected from three stages over the time course of the experiment; early (EM, 0-10% cumulative mortality (CM), 21-25 days post-infection (DPI)), intermediate (IM, 35-55% CM, 28-31 DPI) and late (LM, 75-85% CM, 37-48 DPI) mortality. Viral loads were equal in EM and IM but dropped markedly in LM fish. Gene expression analyses using a 1.8 K salmonid fish cDNA microarray (SFA2.0) and real-time qPCR revealed a large group of genes highly up-regulated across tissues in EM, which were mainly implicated in innate antiviral responses and cellular stress. Despite equal levels of MHC class I in EM and LM, increase of splenic and cardiac expression of immunoglobulin-like genes was found only in LM while a suite of adaptive immunity markers were activated already in IM. The hepatic responses to ISAV were characterized by difference between EM and LM in expression of chaperones and genes involved in eicosanoid metabolism. To develop classification of high and low resistance phenotypes based on a small number of genes, we processed results from qPCR analyses of liver using a linear discriminant analysis. Four genes (5-lipoxygenase activating protein, cytochrome P450 2K4-1, galectin-9 and annexin A1) were sufficient for correct assignment of individuals to EM, LM and uninfected groups, while IM was inseparable from EM. Three of four prognostic markers are involved in metabolism of inflammatory regulators. CONCLUSION: This study adds to the understanding of molecular determinants for resistance to acute ISAV infection. The most susceptible individuals were characterized by high viral replication and dramatic activation of innate immune responses, which did not provide protection. The ability to endure high levels of infection for sustained periods could be associated with lower inflammatory responses while subsequent protection and viral clearance was most likely conferred by activation of adaptive immunity.

SUBMITTER: Jorgensen SM

PROVIDER: S-EPMC2387173 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Gene expression analyses in Atlantic salmon challenged with infectious salmon anemia virus reveal differences between individuals with early, intermediate and late mortality.

Jørgensen Sven Martin SM Afanasyev Sergey S Krasnov Aleksei A

BMC genomics 20080418

<h4>Background</h4>Infectious salmon anemia virus (ISAV) causes a multisystemic disease responsible for severe losses in salmon aquaculture. Better understanding of factors that explain variations in resistance between individuals and families is essential for development of strategies for disease control. To approach this, we compared global gene expression using microarrays in fish dying early and late in the time course following infection from a highly pathogenic ISAV.<h4>Results</h4>Tissues ...[more]

PMID: 18423000

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Project description:Infectious diseases among fish present an important economic burden for the aquaculture and fisheries industries around the world. For example, the infectious salmon anemia virus (ISAV) is known to infect farmed Atlantic salmon (Salmo salar), and results in millions of dollars of lost revenue to salmon farmers. Although improved management and husbandry practices over the last few years have minimized the losses and the number of outbreaks, the risk of new virulent isolates emerging is still a looming threat to the viability and sustainability of this industry. An understanding of the host-pathogen interactions at the molecular level during the course of an infection thus remains of strategic importance for the development of molecular tools and efficient vaccines capable of minimizing losses in the eventual case of a new outbreak. Using a 32 k cDNA microarray platform (cGRASP), we have studied various signaling pathways and immune regulated genes, activated or repressed, in Atlantic salmon head-kidney during the course of an ISAV infection. Gene expressions were measured at 5 different time-points: 6h, 24h, 3d, 7d and 16d post infection to get an overall view of changes as they occurred in time. The earliest time points showed only a few differentially expressed genes in infected fish, relative to controls, although as time progressed, many additional genes involved in key defense pathways were up-regulated including MHC type I, beta-2 microglobulin, TRIM 25 and CC-chemokine 19. During the latest stage of the infection process, many genes related to oxygen transportation were under-expressed, which correlates well with the anemia observed prior to death in Atlantic salmon infected with virulent strains of ISAV. Atlantic salmon smolts from 2 families of Atlantic salmon were IP injected with either 0.1mL of 10e5 TCID50 mL-1 of virus or 0.1mL of sham solution (L15 culture medium) and divided equally in four 1000 L tanks: 2 duplicate tanks containing ISAV injected fish and 2 duplicate control tanks containing sham solution injected fish. Four fish per family were sampled immediately prior to injection. An additional two fish per family per tank (four fish per family total) were sampled at 6h, 24h, 3d, 7d and 16d post injection. Head-kidney was dissected from each fish and used for microarray analysis. ISAV infected Atlantic salmon were compared to non-infected Atlantic salmon for each time-point.

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Gene expression analyses in Atlantic salmon challenged with infectious salmon anemia virus reveal differences between individuals with early, intermediate and late mortality.

Publications

Gene expression analyses in Atlantic salmon challenged with infectious salmon anemia virus reveal differences between individuals with early, intermediate and late mortality.

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