Studies on host-pathogen interactions of infectious salmon anaemia virus

Infectious salmon anemia (ISA) virus (ISAV), an economically important pathogen in marine aquaculture has been classified in the family Orthomyxoviridae, genus Isavirus. ISAV is known to cause overt and fatal systemic infection in farmed Atlantic salmon and asymptomatic infection in both farmed and feral fish. It is well documented that Atlantic salmon that recover from clinical ISA as well as subclinically infected trout and herring can transmit ISAV to healthy Atlantic salmon through cohabitation. The mechanisms of pathogenesis and persistence of ISAV are not adequately studied at the molecular level. This study investigated the host-pathogen interactions of ISAV. Major aspects of this study included the determination of mechanisms of cell death during ISAV infection of fish cells and the exploration of the novel phenomenon of antibody-mediated growth of ISAV in macrophage-like fish cell lines.; Two general pathways known to cause viral cytopathic effect (CPE) are apoptosis and necrosis. In this study, three permissive fish cell lines SHK-1, CHSE-214, and TO were used to determine if ISAV-induced CPE is due to apoptosis or necrosis. Characteristic apoptotic DNA fragmentation was observed only in ISAV-infected SHK-1 and CHSE-214 cells. The apoptosis was confirmed by use of the fragment end labeling assay. ISAV-infected TO cells did not undergo apoptosis but showed leakage of the high mobility group 1 (HMGB1) protein from the nucleus which is characteristic of cells undergoing necrosis. Infected SHK-1 cells did not show leakage of HMGB1 protein. Infection with two different strains of ISAV showed that the induction of apoptosis correlated with the appearance of CPE in SHK-1 cells. These cells did not show caspase-3-like proteolytic activity. The ISAV-induced apoptosis was however inhibited by a pan-caspase inhibitor, Z-VAD-fmk, indicating it is caspase dependent. The ISAV putative PB2 protein and translation products of RNA segment 7 specifically bound caspase-8 in vitro suggesting that these viral proteins may have a role in the ISAV-induced apoptosis.; To study ISAV-antibody interactions, virus neutralization (VN) was performed in the three cell lines using three strains of ISAV and rabbit or fish anti-ISAV sera. (Abstract shortened by UMI.)...