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.