The connection between anemia, immunosuppression, and proliferative disorders caused by avian leukosis viruses will be investigated. An aplastic anemia induced by an avian osteopetrosis virus, MAV-2(0), will be characterized by examining the colonies that grow in a methylcellulose-based semi-solid medium. The nature of a normal cell which restores mitogen responsiveness to MAV-2(0)-infected cell populations will be determined. The identity of a large cell which appears in the spleen of MAV-2(0)-infected chicks developing anemia will be established. The ability of RAV-7 to cause proliferation of lymphoid cells in vitro will be investigated. These studies will clarify the role of avian leukosis viruses in host defense mechanisms. The MAV-2(0) genome will be cloned and used to prepare recombinants between it and RAV-1. Molecular constructs will be injected into chick embryos and the pattern of disease induction established. These studies will identify regions of the MAV-2(0) genome responsible for causing osteopetrosis and other diseases associated with MAV-2(0) infection. The amount and nature of unintegrated viral MAV-2(0) DNA will be determined and correlated with the type of organ-specific changes observed (such as proliferation in the bone, depletion of the bone marrow, hypoplasia in the bursa and thymus). These studies will provide insight into the molecular mechanisms of how avian leukosis viruses cause polyclonal, hyperplastic, and debilitating diseases. Macroscopic and microscopic fibrosarcomas induced by a recombinant avian leukosis virus will be characterized. These tumors appear at high frequency in the muscles of chickens infected with a recombinant virus prepared in the laboratory. The tissue specificity and the nature of the tumor cell appearing in the infected animal will be investigated. The possibility that a new transforming virus is present will be explored by cultivating affected muscle tissue in vitro, observing cultured cells for the appearance of transformed foci, testing for the presence of reverse transcriptase in the supernatant fluid, and determining whether a focus-forming virus is present in supernatant fluids. These studies offer the potential to demonstrate novel interactions of avian leukosis viruses with host onc genes.
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