Significance of 4-O-acetylated sialic acids for the pathogenesis of Infectious salmon anaemia virus (ISAV)
Infectious salmon anaemia (ISA) causes substantial losses in Norwegian aquaculture. The disease occurs after infection with ISAV, an enveloped, segmented, single-stranded, negative sense RNA virus encoding for at least 10 proteins. One of these, surface glycoprotein haemagglutinin esterase, plays an important role in the virus pathology. The enzyme is responsible for binding to and hydrolysis of 4-O-acetylated sialic acids (ISAV receptor) on host cell surfaces including epithelial, vascular endothelial and red blood cells. The progressive loss of 4O-ASA from circulating erythrocytes is correlated with the expression of virus proteins, indicating a repurposing of infected cells by the virus replication machinery. ISA-induced cell surface modulation is thus a critical mechanism during the infection progress.
The aim of the ISATTACH project was to investigate and characterise the sialic acid composition in the epidermal mucus and red blood cells of salmonids, aiming to enhance our understanding of their potential to function as ISA virus receptors.
Using a newly developed liquid-chromatography high-resolution mass spectrometry method for the separation and quantitative detection of different O-ASAs, the sialic acid profiles of different tissues in Atlantic salmon (mucus, gills, heart, red blood cells, plasma) were compared. Furthermore, the specific profiles in Atlantic salmon (Salmo salar) and Rainbow trout (Oncorhynchus mykiss) were determined. Potential effects of the different sialic acids in the mucus on ISAV susceptibility were explored in a number of cell assays, indicating a prominent role of 4O-ASA in ISAV infection.
Internal competence-developing project at the Norwegian Veterinary Institute (2023–2024).