Family–wise resistance to infectious salmon anemia suggests that early systemic recognition protects against disease but not viral transcription

Authors: JOHNSON, AMBER - University Of Maine; Lifgren, Demitri; BOUCHARD, DEBORAH - University Of Maine; TURNER, SARAH - University Of Maine; DELAP, DANIEL - University Of Maine; Polinski, Mark

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/16/2026
Publication Date: 5/20/2026
Citation: Johnson, A., Lifgren, D.L., Bouchard, D.A., Turner, S.M., Delap, D.M., Polinski, M.P. 2026. Family–wise resistance to infectious salmon anemia suggests that early systemic recognition protects against disease but not viral transcription. Frontiers in Immunology. 17. https://doi.org/10.3389/fimmu.2026.1805961.
DOI: https://doi.org/10.3389/fimmu.2026.1805961

Interpretive Summary: Infectious salmon anemia (ISA), caused by infectious salmon anemia virus (ISAV), is one of the most impactful diseases affecting the Atlantic salmon (Salmo salar) aquaculture industry with a capacity to cause severe clinical morbidity and mortality.Herein, a multi–family ISAV exposure experiment was conducted to 1) confirm family–wise resistance in North American Atlantic Salmon, 2) identify if selective breeding efforts focused on growth and sea lice resistance has incidentally impacted ISA resistance, 3) determine viral load changes in multiple tissues to evaluate disease vs virus relationships, and 4) compare gene expression patterns of ISA resistant and susceptible fish to identify potential mechanisms and/or markers of resistance. This study increased our understanding of how salmon respond to ISAV infection after nearly two decades of selective breeding. We corroborated family–based components to ISA resistance while also showing the current breeding priorities (i.e., growth and sea lice resistance) have not likely impacted ISA resistance. In doing so, we also explored the dynamics of ISA vs. ISAV resistance and determined that resistance to ISA and survivorship are not necessarily associated with resistance to ISAV infection and viral replication alone. Given detections of virulent ISAV often require regulatory–mandated action, regardless of manifestation of clinical disease, the distinctions between differential responses associated with ISA (disease) resistance vs those associated with ISAV (infection) resistance are important to consider. Lastly, we successfully deployed dPCR technology for gene expression analysis and found multiple organ and phenotype specific responses, creating a foundation for future research into what host mechanisms contribute most significantly to ISA resistance – highlighting early kidney responses as a differentiator for combating ISA.

Technical Abstract: Introduction: Infectious salmon anemia virus (ISAV), the causative agent of infectious salmon anemia (ISA), is one of the most regulated pathogens affecting Atlantic salmon aquaculture globally. Recent investigations suggest a linkage between the host genome and ISA resistance, identifying a potential for promoting resistance through selective breeding. Herein, we sought to explore the dynamics associated with phenotypic ISA and/or ISAV resistance to better mitigate ISA disease. Methods: Forty families of North American Atlantic salmon were challenged with ISAV to determine family–wise survival, with fish from each family distributed across 16 tanks (one fish per family per tank) and exposed via injection (n = 4 per family) or cohabitation (n = 12 per family). Four additional tanks (1 fish/family/tank) were sampled at either early onset (11–) peak mortality (21– and 35–) or resolution (49– days post challenge) phases of disease. Viral load was determined by RT qPCR and host gene expression by digital PCR in kidney, spleen, heart, and gill. Select spleen samples were also used for RNA–seq transcriptomics. Results: The most resistant (N=12) and susceptible (N=13) families had mean cumulative mortality of 34.3% and 78.5%, respectively. Selective breeding for growth and sea lice resistance (30 families) did not notably impact ISA resistance relative to randomly mated control families (10 families). However, ISA and ISAV resistance were not synonymous – phenotypic ISA resistant and susceptible fish were similarly burdened with virus in all organs screened. Gene expression and RNAseq data identified early viral recognition, particularly in the kidney, as a marker for ISA resistance. Conclusions: Selective breeding for enhanced growth and sea lice resistance did not appear to incidentally impact family–wise resistance to ISA. Phenotypic ISA resistance was at least partially linked to differential gene expression patterns in the kidney highlighting early upregulation of antiviral, inflammatory and endothelial growth factors of resistant fish. However, disease (ISA) resistance was not associated with reduced ISAV transcripts, which showed prolonged high loads in the spleen of all families during infection. These data support early recognition of ISAV in kidney as important in disease mitigation, even when ISAV replication is systemic.