Infection Dynamics and Host Responses to Two IPNV Isolates in Liver of Atlantic Salmon (Salmo salar).

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.