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Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
Published on: September 1, 2015
HIV-1 gp120 primes lymphocytes for opioid-induced, beta-arrestin 2-dependent apoptosis
Jonathan Moorman1, Yi Zhang, Bindong Liu
1Departments of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Abstract:
The mechanisms by which opioids affect progression of human immunodeficiency virus type 1 (HIV-1) infection are not well-defined. HIV-1 gp120 is important in the apoptotic death of uninfected, bystander T cells. In this study, we show that co-treatment of human peripheral blood mononuclear cells (PBMC) with HIV-1 gp120/morphine synergistically induces apoptosis in PBMC. Co-treatment of murine splenocytes from mu opiate receptor knockout mice with gp120/morphine resulted in decreased apoptosis when compared to splenocytes from wild type mice. Co-treatment of human PBMC or murine splenocytes with gp120/morphine led to decreased expression of beta-arrestin 2, a protein required for opioid-mediated signaling. The role of beta-arrestin 2 was confirmed in Jurkat lymphocytes, in which 1) over-expression of beta-arrestin 2 inhibited gp120/morphine-induced apoptosis and 2) RNA interference of beta-arrestin 2 expression enhanced gp120/morphine-induced apoptosis. These data suggest a novel mechanism by which HIV-1 gp120 and opioids induce lymphocyte cell death.
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