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 μ 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 β-arrestin 2, a protein required for opioid-mediated signaling. The role of β-arrestin 2 was confirmed in Jurkat lymphocytes, in which 1) over-expression of β-arrestin 2 inhibited gp120/morphine-induced apoptosis and 2) RNA interference of β-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. © 2009 Elsevier B.V. All rights reserved.
Moorman, J., Zhang, Y., Liu, B., LeSage, G., Chen, Y., Stuart, C., … Yin, D. (2009). HIV-1 gp120 primes lymphocytes for opioid-induced, β-arrestin 2-dependent apoptosis. Biochimica et Biophysica Acta - Molecular Cell Research, 1793(8), 1366–1371. https://doi.org/10.1016/j.bbamcr.2009.05.007