δ-Opioid Suppression of Human Immunodeficiency Virus-1 Expression in T Cells (Jurkat)

Abstract

δ-opioid receptor (DOR) transcripts and binding sites are expressed by lymphocytes and lymphoid cell lines from several species. Direct modulation of lymphocyte function through DORs affects T cell proliferation, interleukin-2 production, chemotaxis, and intracellular signaling. Moreover, in human DOR-transfected T cells (DOR-Ju.1), δ-opioids have been shown previously to mobilize intracellular calcium rapidly, to inhibit forskolin-stimulated cyclic AMP production, and to activate the mitogen-activated protein kinases ERKs 1 and 2. These observations led us to consider whether δ 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, derived from Jurkat cells stably transfected with a cDNA encoding the neuronal DOR, were stimulated with deltorphin or benzamide, 4-[[2,5-dimethyl-4-(2-propenyl)-1-piperazinyl](3-methoxyphenyl)methyl] N-,[2 S[( S∗),2α,5β]]-(9Cl) (SNC-80) prior to the addition of HIV-1. Both deltorphin and SNC-80 concentration-dependently inhibited the production of p24 antigen, an index of HIV-1 expression. Inhibition was maximal with 10 −13–10 −9 M SNC-80 (>60% reduction) or 10 −15–10 −11 M deltorphin (>50% reduction). At higher concentrations, less inhibition of p24 antigen production was found. Naltrindole (NTI, 10 −11 M), a selective DOR antagonist, abolished 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 expressed by CD4 + T cells significantly ( P < 0.05) reduced the expression of HIV-1 by these cells. These findings suggest that opioid immunomodulation directed at host T cells may be adjunctive to standard antiviral approaches to HIV-1 infection.