: A standardized bath challenge of Atlantic salmon reveals distinct infection dynamics and mortality across ten HPR-deleted infectious salmon anaemia virus isolates.
Infectious salmon anaemia virus with highly polymorphic region deletions (ISAV-HPR{Delta}) is classified as pathogenic, yet field outbreaks display wide variation in disease severity. To determine the extent of inherent virulence differences among ISAV-HPR{Delta} isolates, we conducted a standardized freshwater bath challenge in Atlantic salmon using ten isolates, including the high-virulent reference strain NO/Glesvaer/2/90 and nine recent Norwegian field isolates. Cumulative mortality, infection kinetics, tissue viral loads, shedding, and pathological changes were characterised through RT-qPCR, histopathology, immunohistochemistry, and flow cytometry. All isolates established systemic infection, but exhibited pronounced differences in infection dynamics, virus shedding, clinical signs, and pathological outcomes. Cumulative mortality ranged from 15% to 100%, allowing separation of isolates into high- ([≥]90%), moderate- (40-50%), and low-mortality (<20%) categories. Isolates with high mortality showed rapid systemic spread, extensive endothelial infection, and significant pathology compatible with infectious salmon anaemia. Shedding profiles of virus to water differed substantially and were not clearly correlated with cumulative mortality, viral RNA load in tissues or mortality. High ISAV RNA was detected in water for the H16 isolate with [~]10 - 100-fold higher viral RNA than H20 and [A]. VA and S, although giving high mortality (>90%), had much lower (shedding (highest RNA range 1.1 - 3.6^102). Segment 5 and 6 sequencing confirmed that all isolates carried genetic mutations typical of pathogenic ISAV except [A], that have an atypical mutation in the putative protease cleavage site on segment 5. However, these mutations alone did not account for the wide biological continuum of mortality.