HIV-1 gp120 primes lymphocytes for opioid-induced, beta-arrestin 2-dependent apoptosis.
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.
Moorman
Jonathan
J
Departments of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Zhang
Yi
Y
Liu
Bindong
B
LeSage
Gene
G
Chen
Yangchao
Y
Stuart
Charles
C
Prayther
Deborah
D
Yin
Deling
D
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D019390:Arrestins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology / Q000821:virology*; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D034622:RNA Interference; D017450:Receptors, Opioid, mu / Q000172:deficiency / Q000235:genetics; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605254:ARRB2 protein, human; D000701:Analgesics, Opioid; C000605258:Arrb2 protein, mouse; D019390:Arrestins; D015699:HIV Envelope Protein gp120; D017450:Receptors, Opioid, mu; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; C514793:gp120 protein, Human immunodeficiency virus 1; D009020:Morphine