title: Do opioids activate latent HIV-1 by down-regulating anti-HIV microRNAs?
abstract: Researchers have recently demonstrated the presence of anti-HIV-1 microRNAs (miR-28, miR-125b, miR-150, miR-223, and miR-382) in monocytes, macrophages, and CD4+ T cells, which are the primary targets of HIV infection. These miRNAs appear to regulate the level of infectivity of HIV-1 in the target cells, and thus have an impact on HIV-1 latency. The levels of these miRNAs are significantly higher in resting CD4+ T cells than those in active CD4+ T cells, whereas HIV-1 infectivity is greater in active than in resting CD4+ T cells. Similarly, the levels of these miRNAs are significantly higher in monocytes than in macrophages, whereas HIV-1 infectivity is greater in macrophages than in monocytes. Down-regulation or inhibition of the activity of these miRNAs can promote replication of latent HIV-1 in resting CD4+ T cells and in monocytes. Recently, morphine was shown to down regulate the expression of anti-HIV miRNAs (miRNA-28, 125b, 150, and 382) in cultured human monocytes and this effect of morphine was mediated via activation of mu opioid receptors (MOR). In addition, levels of these anti-HIV miRNAs were significantly lower in the peripheral blood mononuclear cells (PBMCs) isolated from heroin-dependent subjects than those from control subjects. These findings raise an important question: Does morphine have potential to activate latent HIV-1 in resting CD4+ T cells and macrophages, including microglia of human subjects maintained on highly active antiretroviral therapy (HAART)? Further research is required to answer this question.
authors.affiliation: Chemistry and Physiological Systems Research Branch, Division of Basic Neuroscience & Behavioral Research, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), 6001 Executive Boulevard Room 4275, MSC 9555, Bethesda, MD 20892-9555, USA. vpurohit@nida.nih.gov
authors.forename: Vishnudutt
authors.initials: V
authors.lastname: Purohit
authors.forename: Rao S
authors.initials: RS
authors.lastname: Rapaka
authors.forename: Joni
authors.initials: J
authors.lastname: Rutter
authors.forename: David
authors.initials: D
authors.lastname: Shurtleff
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000502:physiology*; D017735:Virus Latency / Q000187:drug effects* / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; D035683:MicroRNAs