Studies of mechanisms related to virulence and persistence of IPN virus infection in Atlantic salmon

This project wil address the key mechanisms related to the infection of Atlantic salmon (Salmo salar L) with infectious pancreatic necrosis (IPN) virus, namely virus virulence and virus persistence. Based on the screening of field isolated of IPN virus co llected from clinical outbreak of disease and from carriers, their characteristics as regards ability to induce mortality and persistence will be studies in challenge models of Atlantic salmon fry. Following determination of these characteristics, the dif ferent virus isolates will be sequenced at the genomic level. Motifs will be correlated with virulence and persistence. The reverse genetic system will subsequently be used to generate IPN virus of predicted high and low virulence from cDNA. The virus wil l subsequently be used to infect fish to test the virulence. Along with these studies, the experimentally infected fish will be examined for optake of virus, establishment of infection, spread of virus in internal organs and ability t o induce pathology. Virus persistence will be addressed similarly and at the molecular level, attempts will be made to identify mechanisms of potential importance for virus persistence and reactivation. Mutants of IPN virus will be made by use of the reve rse genetics system and targeted mutagenesis ecperiments will knock out the potential nuclear localization sequences, proteins of importance for transport of virus genome to the cell nucleus. The results will give novel information regarding virulence mec hanisms and aspects of virus persistence. Well-defined virus isolates with know virulence will be available for future studies and a unique research tool will be available for subsequent studies of virus pathogenicity.