A correlation between HIV-1 infection and intravenous opioid abuse has been established, but the drugs' role in HIV-1 induced disease progression is still uncertain. In addition, alkaloid opiates and endogenous opioid peptides have been shown to alter immune function. Therefore, since opioids can modulate immune activity, there is considerable need to understand the role of opioids in the progress of HIV replication. The current practice of administering opioids as analgesics for treatment of pain in HIV-1 infected individuals and the high risk of HIV infection associated with intravenous drug use suggest the importance of investigating the potential interaction between opioids with HIV-1 infected cells. This proposal seeks to identify the mechanism by which opioids modulate HIV-1 replication and expression, and whether opioids act by modulating the expression of chemokines and their receptors. The proposal will be adressed by the following series of experiements. First, the effects of several selective opioids on the expression of both M-tropic and T-tropic strains of HIV-1 will be examined by reverse trancriptase assay, P24 ELISA, and syncytia counts. Second, T cell lines will be engineered to express opioid receptors to further examine the role of opioid receptors on HIV replication. Lastly, the effects of opioids on the expression of the critical chemokines and chemokine receptors during HIV-1 infection will be measured by RNase protection assay.
