The objectives of our Research program are: 1) to determine the basis of the differing biology of Abelson MuLV and the HZ-abl-FeSV; 2) to identify and characterize viral oncogenes in new FeSV strains. The HZ-3590-FeSV has been recently isolated in our laboratories from a multicentric fibrosarcoma. The characterization of the oncogene of this virus revealed homology with the oncogene abl of Abelson-MuLV. Like the A-MuLV it specifies a gag-abl protein with protein kinase activity. In order to understand the differing biology we will investigate the in vivo and in vitro target specificities of this virus and evaluate the contribution of the v-abl insert and of the LTR to the biological properties of this virus. We will clone the integrated HZ-abl-FeSV genome, and we will characterize the v-abl insert. We will determine the sequence relationship between the cat-v-abl and the mouse c-abl and v-abl boundaries. We will sequence the v-abl boundaries and the LTR of this virus. We will construct LTR-gage-abl chemeras in order to investigate whether LTR sequences determine the target specificities of the virus. We will investigate the targets for transformation and consequences of transformation by the abl-FeSV and the in vitro made recombinant viruses: by inoculation into neonate mice and kittens, by in vitro transformation assays, by analyzing the phenotype of the transformants. Three feline sarcoma viruses have been characterized extensively. Two of them contain the oncogene fes, which is related to the avian oncogene fps. A third contains the oncogene fms. We have recently characterized two new FeSV's, the PI-FeSV and the HZ-3590-FeSV. In the PI-FeSV sequences related to the Simian Sarcoma Virus (SSV) oncogene sis were identified. In the HZ-3590-FeSV sequences related to the oncogene abl of Abelson MuLV. More FeSV's are being isolated in W. D. Hardy's Laboratory. We therefore will continue our effort to characterize new FeSV's