The main goal of this project is the elucidation of mechanisms involved in recovery from or persistence of Friend retrovirus complex (FV)-induced erythroleukemia in mice as a model for human retrovirus diseases such as AIDS and certain leukemias. In continuing studies of the role of the H-2 complex in recovery from FV leukemia, we have found that nonspecific immunosuppression induced by FV is strongly influenced by H-2 genotype. In mapping experiments, the H-2D subregion appeared to be critical in this phenomenon. This same subregion is also most important in spontaneous recovery from FV leukemia. However, spontaneous recovery and resistance to immunosuppression were not always associated, since mice of the H-2D(d/b) genotype failed to recover from leukemia even though they did not appear to be immunosuppressed. In a second phase of this project, we have studied the use of a recombinant vaccinia virus vector expressing the FV envelope gene to induce protection against challenge by FV. Before challenge neutralizing antibodies were usually not detectable, and most challenged mice were successfully infected. However, in vaccinated mice rapid recovery from splenomegaly occurred at about 10 days after challenge. Vaccination appeared to protect by priming of virus-specific T cells which then facilitated a rapid secondary immune response after Fv challenge. This secondary response included both neutralizing humoral antibody as well as cytolytic T lymphocytes. The precise role of these effectors in protection is now under investigation.
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