B19 PARVOVIRUS AND ADENO-ASSOCIATED VIRUS

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Our laboratory performs basic and clinical studies of the B19 parvovirus, the only member of the Parvoviridae family pathogenic in humans. Acute infection causes fifth disease, a childhood rash illness and a polyarthralgia syndrome in adults. In patients with underlying hemolysis, acute infection results in transient aplastic crisis. In patients with underlying immunodeficiency, virus infection persists and causes chronic anemia; parvovirus infection is a cause of anemia in patients with AIDS. The virus is tropic for erythroid progenitor cells due to its use of erythrocyte P antigen as a cellular receptor. During the past year, a recombinant parvovirus vaccine reagent, based on recombinant empty capsids produced in a baculovirus system and developed in our laboratory, has entered phase I human volunteer trials. Structural studies of B19 parvovirus empty capsids have tentatively identified the viral binding site for the globoside receptor. In molecular biologic studies, the nonstructural protein, which is responsible for viral replicative functions as well as cytotoxicity, has been shown to interact with the human erk-3 protein kinase, a known transcription regulator. We have also studied two related animal parvoviruses. The entire sequence of simian parvovirus, which causes anemia in cynomolgus monkeys, has been determined and compared to the closely related human virus. Goose parvovirus has been cloned, and its sequence has been shown to be unexpectedly similar to adeno-associated virus, a human member of a Parvoviridae that depends on viral coinfection for its propagation. B19 parvovirus has also been successfully inoculated into cynomolgus monkeys and produced transient bone marrow failure, suggesting an animal model for some forms of human parvovirus infection.