RESEARCH TRAINING IN VIRUS ENTRY STUDIES

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Parvoviruses cause disease in many animals, including humans. The B19 human parvovirus causes the childhood disease Fifth Disease, as well as rarer, but more severe diseases of adults and fetuses. The infectious cellular entry pathway has not been described for any parvovirus. The aims of these studies are to define the infectious entry pathway of canine parvovirus (CPV) into tissue culture cells, with the longer range goal of using this information to understand the mechanisms of host range restriction. The infectious entry pathway of CPV will be dissected by overexpression of dominant interfering mutants of GTPases which regulate specific steps during normal endocytic trafficking. Additionally inhibitory antibodies which block these steps will be microinjected into cells and the effect on viral infectivity assayed. CPV is a recently emerged pathogenic parvovirus that arose by natural mutation of the capsid protein of a cat virus, feline panleukopenia virus (FPV). Three surface regions on the CPV capsid control canine host range, and many mutants with amino acid changes within these regions lose the ability to infect canine cells while still infecting feline cells. Infection by these mutants is blocked during viral entry at a point after cell binding, but prior to viral DNA replication. A comparison of the infectious entry pathways of CPV and its host range mutants in permissive or restrictive cell lines may explain how these regions of the capsid function in different hosts.