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

Phillip K. Peterson, Genya Gekker, James R Lokensgard, Jean M. Bidlack, An Chih Chang, Xingin Fang, Philip S Portoghese

Research output: Contribution to journalArticle

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Abstract

Synthetic κ-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 (≈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-1 infection.

Original languageEnglish (US)
Pages (from-to)1145-1151
Number of pages7
JournalBiochemical Pharmacology
Volume61
Issue number9
DOIs
StatePublished - May 1 2001

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Lymphocytes
Opioid Receptors
HIV-1
Ligands
Antiviral Agents
Macrophages
Neurology
Viruses
Artificial Receptors
CD4-Positive T-Lymphocytes
Nervous System
HIV Infections
Fluorescent Antibody Technique

Keywords

  • AIDS
  • CD4 lymphocytes
  • HIV
  • Opioids
  • U50,488
  • κ-opioid receptor ligands

Cite this

κ-opioid receptor agonist suppression of HIV-1 expression in CD4 + lymphocytes . / Peterson, Phillip K.; Gekker, Genya; Lokensgard, James R; Bidlack, Jean M.; Chang, An Chih; Fang, Xingin; Portoghese, Philip S.

In: Biochemical Pharmacology, Vol. 61, No. 9, 01.05.2001, p. 1145-1151.

Research output: Contribution to journalArticle

Peterson, Phillip K. ; Gekker, Genya ; Lokensgard, James R ; Bidlack, Jean M. ; Chang, An Chih ; Fang, Xingin ; Portoghese, Philip S. / κ-opioid receptor agonist suppression of HIV-1 expression in CD4 + lymphocytes In: Biochemical Pharmacology. 2001 ; Vol. 61, No. 9. pp. 1145-1151.
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