This research is directed at understanding two different levels of interaction between avian retroviruses and their host cell. One level of interaction is at the surface of the cell where the viral attachment protein (the env gene product) interacts with the host cell receptor protein. A second level of interaction is between viral DNA and host DNA, an interaction that occurs as the result of the integration of viral DNA into the host genome. The integration reaction involves a specific cleavage event in viral DNA between tandem copies of the viral LTR sequence. Inappropriate cleavage at the boundary of the LTR may lead to site-specific deletion events in unintegrated and integrated DNA. A replication competent retrovirus shuttle vector will be used to study the process of deletion formation and also the integration reaction. The interaction at the surface of the cell is a major determinant of host range for the virus. Subgroup D avian retroviruses are able to infect mammalian cells, a property of the subgroup D env gene product. Molecular recombinants will be constructed to define the region of the subgroup D env gene that determines mammaltropism. In addition, the major neutralizing epitopes of the env gene product will be identified by isolating viral mutants resistant to neutralizing monoclonal antibodies.