Adeno-associated virus (AAV) is a defective parvovirus which requires helper function from one of two DNA tumor viruses, adenovirus or herpes simplex virus. AAV not only utilizes gene products from these tumor viruses, but it interferes with their growth and with oncogenicity of cells transformed by these viruses. Finally, AAV is able to integrate into host cell DNA in the absence of helper virus and maintain a latent infection. Thus, AAV is of considerable interest both in terms of its ability to maintain itself in host cells and its interaction with its helper viruses. The goal of the research proposed here is to describe these interactions in molecular terms. Specifically, we will: (1) utilize existing adenovirus deletion mutants to more precisely define helper virus functions required for efficient growth of AAV in cultured cells; (2) define the site(s) of interference by AAV with adenovirus growth; (3) study the effects of deletions prepared in an infectious recombinant plasmid on AAV growth; (4) devise a method by which to propagate AAV mutants defective for growth in the presence of wild-type helper virus.
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