The Atlantic salmon, Salmo Salar, is a societally important species of fish, both as a food source and as a component of aquatic biosphere. Its sustainable production is hampered by a wide range of infectious diseases, which is difficult to address due to the lack of in vitro tools to study the disease-host interaction. In this paper, we describe the establishment and characterization of a homogenous Atlantic salmon skin fibroblast (ASSF) cell line. This immortalized cell line grows well in standard media formulations and is capable of migration. It is transcriptionally stable over dozens of passages, and its transcriptome is distinct from other publicly available Atlantic salmon cell lines (SHK1 and ASK). Even though ASSF cells show limited cytopathic effects when challenged with Infectious Pancreatic Necrosis Virus (IPNV) molecular evidence reveals that they are infected and support IPNV production, especially compared to other cell lines like ASK or SHK1. The potential of the ASSF cell line as a tool for Atlantic salmon research is highlighted by its permissibility to genetic manipulation with various methods including CRISPR/cas9, transfection and transduction.

The infectious pancreatic necrosis virus (IPNV) used to be one of the largest loss factors in Atlantic salmon farming. Since 2009, marker-assisted selection for resistance to IPN, tar-geting a single major quantitative trait locus (QTL), has led to a ten-fold decrease in the number of IPN outbreaks in Norway. However, some IPN-related problems remain, due to isolates of the virus which seem to bypass the resistance mechanism of the QTL. We comparatively characterized a classical isolate affected by the IPN-QTL (cIPNV) and an isolate that circumvents the QTL-based protection (rIPNV). Using both in vivo and in vitro challenges, the viral infection dynamics and host responses were evaluated by RT-qPCR and by gene ontology (GO) enrichment analysis from RNA-sequencing data of infected hepatocytes and whole liver. Overall, cIPNV showed rapid replication with pronounced lytic cytopathology and enrichment for DNA damage, apoptosis and cell cycle disruption GO terms, while rIPNV exhibited slower accumulation of viral RNA and a transcriptional footprint consistent with pro-survival states in hepatocytes. While further research is needed to resolve causality of QTL evasion, this work provides a first characterization of the pathogenicity of emerging QTL-insensitive IPNV isolates.

The infectious pancreatic necrosis virus (IPNV) used to be one of the largest loss factors in Atlantic salmon farming. Since 2009, marker-assisted selection for resistance to IPN, targeting a single major quantitative trait locus (QTL), has led to a ten-fold decrease in the number of IPN outbreaks in Norway. However, some IPN-related problems remain, due to isolates of the virus which seem to bypass the resistance mechanism of the QTL. We comparatively characterized a classical isolate affected by the IPN-QTL (cIPNV) and an isolate that circumvents the QTL-based protection (rIPNV). Using both in vivo and in vitro challenges, the viral infection dynamics and host responses were evaluated by RT-qPCR and by gene ontology (GO) enrichment analysis from the RNA sequencing data of infected hepatocytes and the whole liver. Overall, cIPNV showed rapid replication with pronounced lytic cytopathology and enrichment for DNA damage, apoptosis and cell cycle disruption GO terms, while rIPNV exhibited slower accumulation of viral RNA and a transcriptional footprint consistent with pro-survival states in hepatocytes. While further research is needed to resolve the causality of QTL evasion, this work provides a first characterization of the pathogenicity of emerging QTL-insensitive IPNV isolates.