The goal of the proposed research is to elucidate the genomic determinants of virulence in murine leukemia viruses. The strategy for this work is to construct isogenic sets of viruses of AKR origin that differ from one another in specific areas of the genome. the Akv virus is the prototype avirulent strain. A virulent variant SL3-3 that we have isolated is the virulent prototype. The specific aims are: 1. Isolate recombinants of the Akv and SL3-3 viruses using recombinant DNA technology. 2. Test the Akv and SL3-3 recombinants for leukemogenic activity. 3. Determine the nucleic acid sequence of selected regions of the genomes of Akv and AL3-3 viruses that determine the virulence phenotype. 4. Construct isogenic sets of viruses using synthetic oligonucleotides. Futre directions include determination of the biological effets of the genomic changes that lead to the virulent phenotype.