This project involves the biological and molecular characterization of murine leukemia viruses (MuLV) with the aim of understanding host and viral factors involved in the pathogenesis of neoplastic and non- neoplastic sequelae of infection. A continuing major effort involves studies of the complex of viruses responsible for induction of mouse AIDS (MAIDS), a condition characterized by progressive splenomegaly and lymphadenopathy and immune system impairment; polyclonal lymphoid cell proliferation can progress to oligoclonal or clonal expansions of T and B cells. Disease induction is dependent on a defective MuLV (BM5def) whose only product is an altered gag protein encoded by p 15 and p 12 sequences. The presence of replication competent helper virus enhances disease induction markedly but MAIDS can develop in mice of sensitive strains infected helper-free, using stocks prepared in packaging cell lines. The occurrence of disease in such mice is sporadic, however, and latent periods are variably extended and disease may be atypical-- in C57BL mice immunoblastic lymphoproliferative disease presenting primarily in thymus was found in most mice with disease and DNA from affected tissues of all displayed JH rearrangements and integrated BM5def sequences. Induction of MAIDS requires both B and CD4+ T cells, and mice with xid mutation develop much delayed disease. Reconstitution experiments indicate that this is due to abnormalities in conventional B cells, not to the deficit in CD5+ cells also found in xid mice.
