κ-opioid receptor agonist suppression of HIV-1 expression in CD4+ lymphocytes

Synthetic K-opioid receptor (KOR) agonists have been shown to suppress HIV-1 expression in acutely infected macrophages. In the present study, we examined the effects of the KOR ligand trans-3,4-dichloro-N-methyl-N[2-(1 -pyrolidinyl)cyclohexyl] benzeneaceamide methanesulfonate (U50,488) on HIV-1 expression in CD4(+) lymphocytes, the main target cell of this virus. When U50,488 was added to activated CD4(+) lymphocytes, HIV-1 expression was inhibited in a concentration- and time-dependent manner with maximal suppression ( approximate to 60%) at 10(-7) M U50,488, The KOR selective antagonist nor-binaltorphimine (nor-BNI) had no effect by itself on viral expression but blocked the antiviral property of U50,488, suggesting that U50,488 was acting via a KOR-related mechanism. Support for the involvement of KOR was provided by the findings that 34% of activated CD4(+) lymphocytes were positive for KOR, using an immunofluorescence technique, and that seven additional synthetic KOR ligands also inhibited HIV-1 expression. The results of this study broaden understanding of the antiviral properties of KOR ligands to include cells outside of the nervous system and suggest a potential role for these agents in the treatment of HIV-I infection. (C) 2001 Elsevier Science Inc. All rights reserved.