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, ad 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 os erythrocyte P antigen. during the past year, we have identified two new parvovirus diseases. In utero infection can result in congenital anemia. In some children, parvovirus infection can be followed by severe hemolytic anemia in a syndrome termed paroxysmal cold hemoglobinuria. In continuation of vaccine studies, we have demonstrated that synthetic peptides of 20 amino acids, derived from the unique region of the minor capsid protein, elicit neutralizing antibody responses in rabbits. The genetic regulation of B19 parvovirus has been elucidated by identification of functionally active YY1 binding sites in the terminal repeat and promoter regions. An efficient method of purification of YY1 in a baculovirus system has been developed. The cytotoxic effect of the nonstructural protein has been shown to depend on intact nucleotide triphosphate binding regions. We have expanded out parvovirus studies to include adeno-associated virus as a vector for gene therapy. We have demonstrated that adeno-associated virus can transduce a human globin gene into human hematopoietic progenitor cells with high efficiency, resulting in significant protein production. A method to study transient expression of adeno-associated virus in cells under non- selective conditions has been developed.