Activation of unfolded protein response pathway during infectious salmon anemia virus (ISAV) infection in vitro an in vivo

•Infectious salmon anemia virus induce morphological changes indicating unfolded protein response (UPR) in salmon cells.•UPR induced by infectious salmon anemia virus display important differences from classical UPR induced by drugs.•Despite the increased eIF2a phosphorylation ISAV infection does not attenuate the synthesis of interferon and ISGs.

Infectious salmon anemia virus (ISAV) is a salmon pathogen causing serious outbreaks in fish farms world-wide. There is currently no effective commercially available vaccine and there is a need for better understanding of host pathogen interactions with this virus. Various strains can cause both acute and persistent infections and therefore establish a balance with the host immune responses. We have studied host responses to this infection by analyzing the main branches of the unfolded protein response (UPR) in salmon cells in vitro and in tissues from infected fish to gain a better understanding of virus–host interactions. ISAV induce the main symptoms and signaling pathways of UPR (ATF6, PERK and IRE1) without inducing translational attenuation. This may be due to concomitant induction of an important negative feedback loop via the phosphatase regulator GADD34. The host cells can therefore respond with translation of cytokine and antiviral proteins to curb or control infection.