Adeno-associated virus (AAV) is a parvovirus which requires helper function for efficient growth from either one of two tumor viruses, adenovirus or herpes simplex virus, or vaccinia virus. AAV not only utilizes gene products from adenovirus, but it interferes with its growth and with oncogenicity of cells transformed by adenovirus. Finally, AAV is able to maintain a latent infection in the absence of a helper virus by integrating into host cell DNA. 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 long term goal of this proposal is to describe these interactions in molecular terms. The proposal's immediate, specific aims include: (1) Identification of the sequence targets for transactivation of the AAV P5 transcriptional control region and dissection of the mechanism of transactivation; (2) Analysis of the "D" domain within the AAV terminal repeats with emphasis on their role in packaging; (3) Isolation and characterization of AAV temperature-sensitive, linker-insert mutations; and (4) Characterization and elucidation of the mechanism for AAV-induced interference with adenovirus E1A mRNA splicing.