The overall objective is to use caprine arthritis-encephalitis virus (CAEV)- induced disease in goats as a model to study the pathogenetic mechanisms and possible control and treatment of acquired immunodeficiency disease syndrome (AIDS) in humans. The rationale for the project is based on the observation that lentiviruses are associated with states of immunodeficiency and neurologic disorders in several animal species. This observation, coupled with the fact that the human immunodeficiency virus (HIV) is generally considered to be a lymphotropic lentivirus raises the possibility that a large animal lentivirus may serve as a useful model for HIV infection in humans. The specific objectives of the caprine model are to: 1.Evaluate the cellular immune responses in goats exposed to CAEV. 2.Produce and characterize monoclonal antibodies and anti-idiotypes (anti-id) to CAEV. 3. Identify and characterize CAEV receptors on monocytes and synovial membrane cells using anti-id reagents. 4.Test the immunogenicity of anti-id in goats. 5. Determine the major histocompatibility (MHC) types (caprine leukocyte antigen typing) of CAEV-infected and CAEV-free goats. 6. Study the expression of mRNA for proinflammatory cytokines such as interleukin-1 (IL-1), and tumor necrosis factor (TNF-a), in peripheral blood, synovial fluid, and tissue mononuclear cells as well as their production by these cells. 7. Evaluate the glutathione status of CAEV-free and infected goats. 8. Study the infections of gastrointestinal and brain tissues by CAEV. 9. Study the genomic variation of CAEV in goats. 10. Investigate the role of caprine trophoblast protein-1 (cTP-1) in the pathogenic mechanism of CAEV infection. 11. Study of the susceptibility of goats infected with CAEV to infection with the Mycobacterium avium complex.
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