The purpose of the proposed studies is to analyze the mechanisms by which two T-cell tropic retroviruses, the feline leukemia virus (FeLV) and the human T cell leukemia virus (HTLV) affect the immune response of the host. In earlier studies we found that FeLV is a highly immunosuppressive agent, and that the immune response is extremely important in preventing the development of both FeLV-induced leukemia and the viremia associated with opportunistic infections. In more recent studies we showed that people in southern Japan with acute infectious diseases have a greatly increased probability of being HTLV carriers, and that asymptomatic hemophiliacs that were exposed to HTLV have decreased levels of T helper lymphocytes when compared to asymptomatic hemophiliacs that were not exposed to HTLV. In the current proposal we plan to examine cats with natural and laboratory-induced FeLV infections to determine how their lymphocyte subpopulations may be altered, and how this may be correlated with the level of immune response to the synthetic peptide (T,G)AL. We will examine the biological and biochemical properties of FeLV's that are regularly associated with immunosuppression and compare these to the properties of prototype strains of FeLV that are not associated with immunosuppression. In particular, we will analyze the soluble shed FeLV-related proteins that are excreted by various FeLV-infected cats, and try to determine how the presence of these proteins in the plasma of FeLV-infected cats is correlated with the ability of the animal to mount an immune response. In somewhat parallel studies we will examine the lymphocyte subpopulation status of HTLV-infected carriers, including patients with infectious diseases from the endemic area of Japan, asymptomatic hemophiliacs, and control healthy carriers and HTLV-uninfected individuals with the same infectious diseases. Following the same general patterns of experiments that we proposed for the FeLV system above we will also analyze the T cell subset tropism and the biological and biochemical properties of HTLV's isolated from individuals with immunosuppression. We will also examine the plasmas of HTLV-infected individuals of the different classes mentioned above for the presence of shed HTLV-related proteins. Such proteins will be characterized and qualitatively and quantitatively analyzed for their relationship to immune function.
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