DESCRIPTION: (Applicant's Abstract) Unlike HIV-1, HTLV-I infection requires and induces Type I cytokines, such as IL-2 and IFNy. The finding that chronic users of Type I cytokine-repressing opiates are almost 70-fold more likely to acquire HTLV-I is provocative in this sense, as is the greater incidence of HTLV-I disease in coinfected AIDS patients. HTLV-I infection may also be enhanced by the use of immunostimulatory therapies targeting AIDS patients. It is postulated that HTLV-I can overcome the repressive effects of morphine or HIV-1 by inducing a shift from Type II to Type I cytokine production. This shift is for the benefit of the virus and involves the deregulated activation of transcription factors relevant to IL-2 and IFNy synthesis. To test this hypothesis, the following specific aims will be pursued. Aim 1: To determine the ability of HTLV-I to modify Type I versus Type II (IL-4, IL-6) cytokine production in opiate-treated human T cells. Aim 2: To determine the ability of HTLV-I to reverse HIV-1 cytokine repression, and to determine if HTLV-I infection is actually enhanced during coinfection with HIV-1, in opiate-treated cells. Aim 3: To determine the ability of morphine (an immunosuppressive opiate) and methionine enkephalin (an immunostimulant opioid used in AIDS-targeted experimental therapies) to modify HTLV-I infection and replication in human T cells.