This project involves the isolation and characterization of C-type murine leukemia viruses (MuLVs), with particular emphasis on biological and molecular factors important for infection of mice, specification of target cells, and induction of neoplastic or other disease. The primary subject of current study is the complex of viruses (LP-BM5 MuLVs) responsible for induction of murine AIDS. Sensitive strains of mice infected with LP-BM5 virus, a mixed stock containing a 4.9Kb replication defective MuLV genome (BM5def) and B-tropic replication competent ecotropic and MCF helper MuLVs, develop progressive lymphproliferative disease and impairment of immune system functions, the pathogenetic process requiring the defective viral genome and both B cells and CD4+ T cells. When virus stocks obtained by co-transfection of cells with molecularly cloned BM5def and helper BM5 ecotropic MuLV DNAs were used to infect mice of the sensitive C57BL strains, disease developed that was in all immunologic and histopathologic respects identical to that induced by the original uncloned virus mixture. Differences noted were delayed onset and progression of disease and lower frequency of spleen cells producing helper virus. Coinfection of mice with additional helper virus, particularly MCF MuLV, resulted in enhancement of the degree of splenomegaly and lymphadenopathy and modest but consistent increase in frequency of ecotropic virus producing cells. Further studies of the molecularly cloned BM5def genome have revealed that while cell lines derived following successful transfection may contain the same size extra-genomic band that is detected using a BM5def probe in Southern blots of lymphoid tissues from infected mice, lines also occur with widely different restriction enzyme patterns of hybridizing fragments. Virus recovered from some of these lines after infection with helper virus induces MAIDS which may be associated with structurally altered genome.
