DELTA-OPIOID SUPPRESSION OF HUMAN IMMUNODEFICIENCY VIRUS-1 EXPRESSIONIN T-CELLS (JURKAT)

delta-opioid receptor (DOR) transcripts and binding sites are expresse d by lymphocytes and lymphoid cell lines from several species. Direct modulation of lymphocyte function through DDRs affects T cell prolifer ation, interleukin-2 production, chemotaxis, and intracellular signali ng. Moreover, in human DOR-transfected T cells (DOR-Ju.1), delta-opioi ds have been shown previously to mobilize intracellular calcium rapidl y, to inhibit forskolin-stimulated cyclic AMP production, and to activ ate the mitogen-activated protein kinases ERKs 1 and 2. These observat ions led us to consider whether delta agonists modify T cell functions , thus affecting the expression of human immunodeficiency virus-1 (HIV -1) by CD4(+) T cells. To test this hypothesis, DOR-Ju.1 cells, derive d from Jurkat cells stably transfected with a cDNA encoding the neuron al DOR, were stimulated with deltorphin or benzamide, penyl)-1-piperaz inyl]3-methoxyphenyl)methyl]N-,[2S [(S ),2 alpha,5 beta]]-(9Cl) (SNC- 80) prior to the addition of HIV-1. Both deltorphin and SNC-80 concent ration-dependently inhibited the production of p24 antigen, an index o f HIV-1 expression. Inhibition was maximal with 10(-13)-10(-9) M SNC-8 0 (>60% reduction) or 10(-15)-10(-11) M deltorphin (>50% reduction). A t higher concentrations, less inhibition of p24 antigen production was found. Naltrindole (NTI, 10(-11) M), a selective DOR antagonist, abol ished the inhibitory effects of 10(-9) M SNC-80, whereas 10(-13) M NTI partially reversed the effect of SNC-80. Thus, activation of DORs exp ressed by CD4(+) T cells significantly (P < 0.05) reduced the expressi on of HIV-1 by these cells. These findings suggest that opioid immunom odulation directed at host T cells may be adjunctive to standard antiv iral approaches to HIV 1 infection. BIOCHEM PHARMACOL 56;3:289-292, 19 98. (C) 1998 Elsevier Science Inc.