author's abstract.) AIDS is a disease affecting many organs; notably, those of the immune, nervous, and neuroendocrine systems. The overall hypothesis in this application is that the production of neuroendocrine hormones and/or responsiveness to these molecules by lymphocytes is altered by HIV infection and that this may mediate some of the endocrine and immune abnormalities seen in AIDS. Previously, these investigators found that the AIDS virus, HIV, induces the neuroendocrine hormone, adrenocorticotrophin (ACTH), in lymphocytes. Further, they found structural and functional similarity between CRF and the major envelope protein of HIV, gp120. Apparently, therefore, this structural similarity reflects function. In the research proposed, the investigators will characterize this homology in structural and functional terms in order to determine the ability and likelihood that HIV's lymphoid and non-lymphoid effects are through CRF receptors. The effects of HIV infection on hormone production and response in populations of neuroendocrine and lymphoid cells will be studied at both the cellular and molecular levels. These studies should provide new insight into the role HIV infection of the immune system has on the endocrine abnormalities seen with AIDS and may suggest new therapies either to control the infection or to treat the debilitating systemic alterations.
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