Studies of virulence mechanisms and host responses to infection with piscine myocarditis virus (PMCV)

The studies in this period have focused on the ORF-3 encoded protein and host responses and risk factors for coinfection of PRV and PMCV. ORF- 3 protein is cytotoxic and causes complete lysis of cells and bacteria when expressed. We know which parts of the protein are crucial for this property and the cellular degradation of the protein appears to play an important role in that it becomes toxic. The effect is related to damage to the cellular membranes and the protein probably has significance for the release of virus from infected cells. Studies have shown that co-infection in vivo with PRV and PMCV leads to increased damage in the heart , especially of the epicardium , with thickening and intense inflammation cell infiltration . PRV does not seem to inhibit the development of damage caused by PMCV , contrary to what seems to be the case with other viral infections .

The aetiology of CMS was defined through the identification of the causative agent, piscine myocarditis virus (PMCV). Built on this new knowledge, we propose a joint research project between the Norwegian School of Veterinary Science and NOFIMA to further explore the pathogenic traits of the virus with an approach to study the detailed infection mechanisms in vitro as well as host immune and immune-related responses to infection plus environmental impact on disease susceptibility. In doing so we will be a ble to pinpoint risk factors associated with the infection, knowledge that can be used for disease prevention and control in an aquaculture setting. The methodology employed will include reverse genetics with the purpose to obtain a unique tool for in vit ro and in vivo studies of infection mechanisms. We will further characterize the virus proteins in terms of immunochemical properties and the viral entry and exit strategies. To obtain a detailed understanding of the virus protein characteristics, the cry stal structure of the surface proteins will be elucidated at Ångstrom level through collaboration with Institut Pasteur in France and Dr. Felix Rey. In vivo studies will be performed with the purpose of understanding host responses to infection and partic ularly the importance of high and low responders in terms of immune responses possibly correlating with severity of heart pathology. Further attempts will be made to pinpoint possible links with high and low stress response patterns in groups of salmon, b ased on swimming tests. Possible interaction with environmental factors like hypoxia and the interaction between PMCV and another myocarditis virus (piscine reovirus causing HSMI). The results emerging from this project will provide new knowledge of infec tion mechanisms and host responses to infection and will provide tools for better disease control and prevention.