Comparison of Atlantic salmon individuals with different outcomes of cardiomyopathy syndrome (CMS)

Abstract

BackgroundCardiomyopathy syndrome (CMS) is a severe disease of Atlantic salmon (Salmo salar L.) associated with significant economic losses in the aquaculture industry. CMS is diagnosed with a severe inflammation and degradation of myocardial tissue caused by a double-stranded RNA virus named piscine myocarditis virus (PMCV), with structural similarities to the Totiviridae family. In the present study we characterized individual host responses and genomic determinants of different disease outcomes.ResultsFrom time course studies of experimentally infected Atlantic salmon post-smolts, fish exhibited different outcomes of infection and disease. High responder (HR) fish were characterized with sustained and increased viral load and pathology in heart tissue. Low responder (LR) fish showed declining viral load from 6–10 weeks post infection (wpi) and absence of pathology. Global gene expression (SIQ2.0 oligonucleotide microarray) in HR and LR hearts during infection was compared, in order to characterize differences in the host response and to identify genes with expression patterns that could explain or predict the different outcomes of disease. Virus-responsive genes involved in early antiviral and innate immune responses were upregulated equally in LR and HR at the first stage (2–4 wpi), reflecting the initial increase in virus replication. Repression of heart muscle development was identified by gene ontology enrichment analyses, indicating the early onset of pathology. By six weeks both responder groups had comparable viral load, while increased pathology was observed in HR fish. This was reflected by induced expression of genes implicated in apoptosis and cell death mechanisms, presumably related to lymphocyte regulation and survival. In contrast, LR fish showed earlier activation of NK cell-mediated cytotoxicity and NOD-like receptor signaling pathways. At the late stage of infection, increased pathology and viral load in HR was accompanied by a broad activation of genes involved in adaptive immunity and particularly T cell responses, probably reflecting the increased infiltration and homing of virus-specific T cells to the infected heart. This was in sharp contrast to LR fish, where recovery and reduced viral load was associated with a significantly reduced transcription of adaptive immunity genes and activation of genes involved in energy metabolism.ConclusionsIn contrast to LR, a stronger and sustained expression of genes involved in adaptive immune responses in heart tissue of HR at the late stage of disease probably reflected the increased lymphocyte infiltration and pathological outcome. In addition to controlled adaptive immunity and activation of genes involved in cardiac energy metabolism in LR at the late stage, recovery of this group could also be related to an earlier activation of NOD-like receptor signaling and NK cell-mediated cytotoxicity pathways.

Effects of functional feeds on the lipid composition, transcriptomic responses and pathology in heart of Atlantic salmon (Salmo salar L.) before and after experimental challenge with Piscine Myocarditis Virus (PMCV)

“…The time-courses for the development and resolution of histopathology and immune gene responses were similar to those observed previously [10, 11]. In addition, there were correlations between the expression of genes related with immune responses, viral load and heart lesions, in agreement with Timmerhaus et al [10].…”

“…Put another way, the functional feeds generally lowered the immune/inflammatory status prior to viral challenge and, in doing so, delayed and moderated the response to the infection. This was supported by the recent finding that showed low-responder fish to CMS, which developed high infection levels in the absence of cardiac pathology, had ablated expression of adaptive immunity genes and genes involved in T cell responses [11]. However, it must be emphasised that immune and inflammatory responses are essential components of the host defence against infections [45].…”

“…The qPCR primer sequences (Additional file 3: Table S2) previously described by Timmerhaus et al [11] were employed following the same procedure and from the same RNA samples used for the validation of the microarray (as described above).…”

Cardiomyopathy syndrome in Atlantic salmon Salmo salar L.: A review of the current state of knowledge

“…Despite a strong correlation between viral load and severity of cardiac lesions, Timmerhaus and coworkers noticed that not all infected fish developed significant cardiac pathological condition during their challenge (Timmerhaus et al., ). In a second study of the sample set, fish that had developed severe cardiac lesions were grouped as high responders (HR), while fish without significant cardiac lesions were grouped as low responders (LR) (Timmerhaus et al., ). The challenged fish mounted similar antiviral and innate immune responses the first weeks post‐challenge (Timmerhaus et al., , ).…”

“…In a second study of the sample set, fish that had developed severe cardiac lesions were grouped as high responders (HR), while fish without significant cardiac lesions were grouped as low responders (LR) (Timmerhaus et al., ). The challenged fish mounted similar antiviral and innate immune responses the first weeks post‐challenge (Timmerhaus et al., , ). From about 6 wpi, the fish group diverged in the two main directions.…”