Dr. Parrish and his collaborator Dr. Michael Rossman propose to study the three dimensional structure, assembly, and capsid-related functions of autonomous parvoviruses. They will focus on canine parvovirus (CPV), the closely related feline panleukopenia parvovirus (FPV), and the more distantly related human Bl9 parvovirus. Bl9 is the etiological agent off childhood fifth disease and of transient aplastic crises. The investigators propose to study several biological processes associated with viral infection, including cell attachment, penetration, uncoating, assembly and antibody production. The studies proposed include X-ray crystallographic studies of CPV, FPV, and Bl9 as well as various mutants of these viruses expressed either as viable viruses or self-assembled empty capsids. In addition, complexes of FAbs and viruses will be studied to determine the mechanisms of antibody neutralization. Mutants will also be isolated in the viral capsid proteins to determine the residues important for capsid assembly. Intermediates of capdis assembly or sub-assembly will be examined to define the types of contacts that determine the threefold, twofold, and fivefold related interactions between the various VP2 molecules. The mutants will also be used to identify caps id residues important for receptor binding and the X-ray structures of mutants defective for receptor binding will be solved. Finally, a variety of techniques will be used to identify and clone the cellular receptor for parvoviruses. The receptor will then also be studies by genetic and structural methods.
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