Comparison of transcriptomic responses to pancreas disease (PD) and heart and skeletal muscle inflammation (HSMI) in heart of Atlantic salmon (Salmo salar L).

Pancreas disease (PD) and heart and skeletal muscle inflammation (HSMI) are viral diseases associated with SAV (salmonid alphavirus) and PRV (piscine reovirus), which induce systemic infections and pathologies in cardiac and skeletal muscle tissue of farmed Atlantic salmon (Salmo salar L), resulting in severe morbidity and mortality. While general features of the clinical symptoms and pathogenesis of salmonid viral diseases are relatively well studied, much less is known about molecular mechanisms associated with immunity and disease-specific changes. In this study, transcriptomic analyses of heart tissue from PD and HSMI challenged Atlantic salmon were done, focusing on the mature phases of both diseases at respectively 28-35 and 42-77 days post infection. A large number of immune genes was activated in both trials with prevalence of genes associated with early innate antiviral responses, their expression levels being slightly higher in PD challenged fish. Activation of the IFN axis was in parallel with inflammatory changes that involved diverse humoral and cellular factors. Adaptive immune response genes were more pronounced in fish with HSMI, as suggested by increased expression of a large number of genes associated with differentiation and maturation of B lymphocytes and cytotoxic T cells. A similar down-regulation of non-immune genes such as myofiber and mitochondrial proteins between diseases was most likely reflecting myocardial pathology. A suite of genes important for cardiac function including B-type natriuretic peptide and four neuropeptides displayed differential expression between PD and HSMI. Comparison of results revealed common and distinct features and added to the understanding of both diseases at their mature phases with typical clinical pictures. A number of genes that showed disease-specific changes can be of interest for diagnostics.

MyD88 interacts with interferon regulatory factor (IRF) 3 and IRF7 in Atlantic salmon (Salmo salar): transgenic SsMyD88 modulates the IRF-induced type I interferon response and accumulates in aggresomes.

MyD88 is an intracellular adaptor protein that transmits signals downstream of immune receptors such as the IL-1 receptor and the majority of the known mammalian toll-like receptors. Homologs of MyD88 have been identified in many vertebrate species; however, the adaptor has been studied mostly in mammals, and little is known about its function in lower vertebrates. The results presented in the current paper demonstrate, for the first time, that the teleost MyD88, through its Toll/Interleukin-1 receptor domain, interacts with SsIRF3 and two SsIRF7 paralogs: transcription factors that are critically involved in the virus-induced IFN responses. The data further highlight the potential of transgenic SsMyD88 to modulate the IRF-induced type I IFN response as the adaptor synergized with SsIRF3 to activate IRF-E/IFN-stimulated response element-containing reporter gene constructs and endogenous myxovirus resistance homolog expression. Microscopy analyses demonstrated that, similar to mammalian MyD88, both endogenous and transgenic SsMyD88 accumulated in intracellular aggregates. However, unlike the endogenous SsMyD88 clusters, which co-localized with endocytosed CpGs and probably represented myddosomes, overexpressed SsMyD88 accumulated in aggresomes. Although these structures accumulated ubiquitinated proteins, they did not associate with the autophagosome markers p62 and light chain 3-like protein, indicating that they are most likely classical aggresomes rather than aggresome-like induced structures, aggregates of ubiquitinated proteins induced by toll-like receptor/MyD88 signaling in antigen-presenting cells. The significance of the accumulation of transgenic MyD88 in aggresomes is currently unknown; nevertheless it is tempting to speculate that it might represent a defense mechanism against the potentially harmful effects of excessive MyD88 signaling.