Viral attachment to a specific cellular receptor is a critical initial event in infection, often influencing virus host ranges and tissue tropisms. Parvoviruses infect humans and other animals causing serious diseases, including erythema infectiosum, transient aplastic crisis and fatal diarrheas of neonates. Canine parvovirus (CPV) first emerged as a new virus of dogs in 1978, and genetic studies show that host range differences between CPV and its probable ancestor, feline panleukopenia virus (FPV), are determined by only a few changes in the surface of the capsid.
The aims of these studies are to define the molecular interactions between CPV and its cellular receptor(s), identifying and characterizing the molecules used for viral attachment, and defining the complementary binding site on the viral capsid. Regions on the CPV capsid surface mediating binding to cell and erythrocyte membrane receptors will be defined by site-directed mutagenesis. Capsids will be expressed and assembled from the engineered protein and analyzed for their binding properties. The cellular receptor used by the virus for cell binding and entry will be characterized in biochemical studies. Techniques used to identify and isolate the receptor will include virus binding assays and the generation of antibodies to cell surface proteins, with subsequent immuno-affinity purification. If the receptor is a protein, as preliminary studies suggest, the gene will be isolated by cDNA cloning and subjected to molecular analysis. In order to develop models for pathological events which result in depletion of lymphoid cells in CPV infected dogs, CPV-receptor stimulated intracellular events in lymphocytes will also be examined in vitro.
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