Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: Experimentally infected Atlantic salmon post-smolts exhibited different outcomes of disease (CMS). 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 analyses were performed to compare these groups. 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 indicated the early onset of pathology. By six weeks both responder groups had comparable viral loads, while increased pathology was observed in HR fish. This was reflected by induced expression of genes implicated in apoptosis and cell death, 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. Atlantic salmon post smolts (average weight 50g) were challenged with the putative CMS causing pathogen (PMCV). Heart was sampled from challenged and control fish at 2, 4, 6, 8 and 10 wpi. Heart pathology was detectable earliest at 6 wpi and from this time-point, individuals were assigned to HR and LR.

ORGANISM(S): Salmo salar

SUBMITTER: Aleksei Krasnov

PROVIDER: E-GEOD-36860 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Cardiomyopathy syndrome (CMS) is a disease associated with severe myocarditis in adult Atlantic salmon (Salmo salar L.), which is presumably caused with a double-stranded RNA virus (piscine myocarditis virus; PMCV). This study addressed the host immune response in Atlantic salmon during experimentally induced CMS as assessed by microarray transcriptome profiling. Post-smolts were infected by intraperitoneal injection of PMCV and developed cardiac pathology consistent with CMS. From analysis of heart samples at several time points and different tissues at early and clinical stages by oligonucleotide microarrays, six gene sets representing a broad range of immune responses were identified. Histopathological examination of cardiac tissue showed myocardial lesions from 6 weeks post infection (wpi) that peaked at 8-9 wpi and was followed by a recovery. Viral RNA was detected in all organs from 2 wpi. The highest and equal viral load was observed in heart, spleen and kidney, peaking at 8-9 wpi. Strong and systemic induction of antiviral and IFN-dependent genes from 2 wpi that leveled off during infection, was followed by a biphasic activation of pathways for B cells and MHC antigen presentation, both peaking at clinical pathology. This was preceded by a distinct cardiac activation of complement at 6 wpi. Most severe cardiac pathology and peak viraemia coincided with a cardiac-specific activation of T cell responses dominated by genes involved in effector CD8 cell responses and splenic induction of complement. These changes preceded the reduction in viral load and pathology, suggesting an important role of cytotoxic T cells for viral elimination in infected heart. Atlantic salmon post-smolts (average weight 50g) were challenged with the putative CMS-causing pathogen (PMCV). Hearts were sampled from challenged and control fish at 2, 4, 6, 8, 9 and 10 wpi. Pools of equal amounts of total RNA from three fish hearts each were combined and hybridized against control pools of 8 to 10 fish hearts per time point. Spleen, liver, mid-kidney, red blood cells (RBC) and peripheral blood leukocytes (PBL) were analyzed at 4 wpi (latest time point before clinical stage) and 8 wpi (peak pathology). The samples of infected fish were labeled with Cy5 and hybridized to control samples from the same time-points labeled with Cy3. Competitive hybridization to the arrays was followed by washing, scanning, image analysis, and data analysis. Selected genes were analyzed with RT-qPCR.

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

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