This project is designed to do two things: first, to test the hypothesis that changes in steroid hormone effects are involved in the direct and indirect cytopathicity of HIV; and second, to use a DNA response element for glucocorticoids as a cis-active control over HIV genes to determine their functions quantitatively. Steroid hormones have profound effects on lymphoid cells directly and also indirectly, through influences on many peptide hormones and their receptors. We will investigate the effects of steroids on peripheral blood lymphoid cells of HIV infected individuals and on several infected cell lines. This will require studies of cellular effects of steroids, analysis of steroid receptors, and examination of the interactive effects of steroids with several peptide hormones and their receptors. Limited reports raise the possibility that HIV is glucocorticoid-inducible. We will thoroughly test this possibility. The exact function of several HIV genes is unknown, as are the quantitative relationships between specific gene products and overall HIV replication and cytopathicity. We will place the glucocorticoid response element from the MMTV LTR in a cis relationship to HIV or specific HIV genes, to provide glucocorticoid-regulatable HIV genes for study in transfected cells. Our clonal lines of CEM cells with known lesions in the glucocorticoid response system, should be of particular value in these studies.
