The transcriptomic response of ISAV and IPNV infection in Atlantic salmon cells

Abstract Interferon alpha (IFNa) is critical in mediating host cell antiviral defenses. In Atlantic salmon, IFNa mediates protective responses against infectious salmon anemia virus (ISAV) and infectious pancreatic necrosis virus (IPNV), but this antiviral response and the associated changes in molecular physiology remain unclear. This study examines the antiviral response in Atlantic salmon head kidney (SHK-1) cells infected with ISAV or IPNV following IFNa treatment and showed significant upregulation of key antiviral genes, isg15 and mx . Moreover, transcriptomic analysis identified upregulation of different viral sensing receptor pathways including RIG-I-like, NOD-like, and Toll-like receptor signaling and innate immune pathways, along with metabolic pathways essential for immune cell function. Despite reductions in viral loads in IFNa-treated cells, viral persistence was observed, suggesting that ISAV and IPNV may employ evasion mechanisms. Among other genes, irf1-2 (a paralogue of IRF1 : interferon regulation), important for interferon regulation, and c25ha , linked to primary bile acid biosynthesis, were significantly upregulated in IPNV-infected cells but did not respond in ISAV-infected cells, suggesting different host–pathogen interaction strategies. Furthermore, the upregulation of axin-2-like , a key regulator in the Wnt signaling pathway, in ISAV-infected cells suggests that ISAV may exploit this pathway to evade the host immune system. These findings provide new insights into the distinct genetic responses elicited by ISAV and IPNV and highlight the complexity of IFNa-mediated host defense mechanisms in salmon.