| Summary: | This thesis focuses on infection kinetics, infected cell types, viral shedding, and specific immune responses in persistently Piscine orthoreovirus-1 (PRV-1) infected Atlantic salmon. The aim is to enhance the understanding of viral pathogenesis. PRV-1 is ubiquitous in Norwegian Atlantic salmon (Salmo salar) aquaculture. PRV-1 causes an acute infection of erythrocytes of Atlantic salmon and thereafter the virus spreads to cardiomyocytes which induce the disease of heart and skeletal muscle inflammation (HSMI). PRV-1 is not cleared by the Atlantic salmon immune system after acute infection and persists life-long in the host. In Atlantic salmon focal melanized changes (black spots) of white skeletal muscle tissues, which histologically appear as granulomatous structures, are commonly observed in the fillet and is associated with chronic PRV-1 infection. Even if PRV-1 associates with the development of melanized focal changes (black spots), the causal relationship is questionable. Experimental challenge studies shows that PRV-1 establishes a productive and persistent infection at low level till the end of the trial. PRV-1 transcription level was high in blood cells in the acute phase and in the kidney during the persistent phase. PRV-1 caused plasma viremia that started in the acute phase and lasted for at least 18 weeks, i.e. the end of the experiment. In situ hybridization assays identified PRV-1 infection of Macrophage colony-stimulating factor receptor (MCSFR) positive macrophages in kidney and spleen and Erythropoietin receptor (EPOR) positive erythroid progenitor cells in the kidney, in both acute and persistent phases. The infected erythroid progenitor cells may represent a possible reservoir for PRV-1 as a continuous source of new generated erythrocytes. Macrophage polarization response (M1/M2) and cell mediated immune response was assessed both in HSMI and black spots formation. M1 macrophages were dominant in the red spots and almost all co-stained for PRV-1. In spots assessed as “late phase” of red spots ...
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