Haemorrhagic kidney syndrome may not be a variation of infectious salmon anaemia

Haemorrhagic kidney syndrome (HKS) of Atlantic salmon is a condition of unknown aetiology that was responsible in the late 1990's for large scale losses in Eastern Canada in sea-caged fish. Lesions included renal interstitial haemorrhage, plus acute renal tubular necrosis with eosinophilic casts. Affected fish were shown to have erythrocyte inclusion body virus (EIBS) but the significance of this infection was unknown at the time. Following the initial report describing this syndrome, data were published showing that infectious salmon anaemia virus (ISAV) was involved with HKS, that lesions typical of HKS could be reproduced using extracts of kidney from fish with HKS, and that these extracts contained ISAV. Even though no liver lesions were ever seen (the hallmark of ISA) the conclusion was reached that HKS was a pathological variation of ISA. Piscine orthoreovirus (PRV) is an emerging viral pathogen of both Atlantic and Pacific salmon. In the former, it is causally linked to heart and skeletal muscle inflammation (HSMI), while in Pacific salmon, a range of jaundice syndromes and distinctive renal tubular necrosis are reported. The similarity of the renal lesions in Pacific salmon to those seen in HKS prompted a re-evaluation of HKS, using in-situ hybridization to identify and localize both PRV and ISAV, using the archived material from which HKS was originally described. We show here the presence of both ISAV and PRV in affected tissues, concentrated in lesions. These findings show that fish with HKS had a dual viral infection, and that HKS was not, therefore, necessarily due to ISAV alone. Given the similarity between the renal lesions in HKS and those in chinook salmon with PRV, these findings also suggest that PRV was a more plausible aetiological candidate. It is just as likely, however, that both viruses were required, and that they acted in a synergistic fashion. The lesions in renal tubules in HKS, partly driven by haemoglobin and partly by one or both viruses, probably led to release of locally high levels of vasoactive factors that were able to target the peritubular capillaries of the renal portal system, leading to necrosis and interstitial haemorrhage. •Haemorrhagic kidney syndrome (HKS) was a disease that devastated farmed Atlantic salmon in Canada in the late 1990's.•The original archived material from which HKS was described and defined was re-examined using in-situ hybridization techniques.•This approach showed that, associated with the r