Inhibition of Anti-HIV MicroRNA Expression

Abstract

Several micro RNAs (miRNAs) have the ability to inhibit HIV replication in target cells. Thus, we investigated the impact of opioids (morphine and heroin), widely abused drugs among people infected with HIV, on the expression of cellular anti-HIV miRNAs in monocytes. We found that morphine-treated monocytes expressed lower levels of cellular anti-HIV miRNAs than untreated cells. In addition, morphine treatment of monocytes compromised type I interferon (IFN)-induced anti-HIV miRNA expression. These findings paralleled the observation that morphine treatment of monocytes enhanced HIV replication. These morphine-mediated actions on the anti-HIV miRNAs and HIV could be antagonized by the opioid receptor antagonists (naltrexone or Cys2, Tyr3, Arg5, Pen7-amide). Furthermore, the in vitro impact of morphine on miRNA expression was confirmed by the in vivo observation that heroin-dependent subjects had significantly lower levels of anti-HIV miRNAs (miRNA-28, 125b, 150, and 382) in peripheral blood mononuclear cells than the healthy subjects. These in vitro and in vivo findings indicate that opioid use impairs intracellular innate anti-HIV mechanism(s) in monocytes, contributing to cell susceptibility to HIV infection. (Am J

Morphine increases hippocampal viral load and suppresses frontal lobe CCL5 expression in the LP-BM5 AIDS model

“…Mediated largely by IFN-α and IFN-β, type 1 interferon signaling increases cellular resistance to viral infection, facilitates interaction of infected cells with immune cells via increased MHC I expression, and impairs viral replication (Paul et al, 2007). Disruption of IFN-α, β signaling has been observed in morphine-treated human monocytes, leading to increased HIV-1 replication (Wang et al, 2011). Similarly, LP-BM5 infection itself was shown to disrupt the type 1 interferon response in splenocytes and other peripheral organs (Cheung et al, 1991; Pitha and Biegel, 1988).…”

“…However, other in vitro studies showed that morphine decreased Tat-induced production of interleukin (IL)-8 by astrocytes (Reddy et al, 2012) and the production of TNF-α, IL-6, and CCL2/MCP-1 (monocyte chemoattractant protein-1) by microglia (Jadwiga Turchan-Cholewo et al, 2009). Morphine also disrupts type 1 interferon signaling, leading to a dysregulated cellular antiviral response and facilitating increased viral replication (Cheung et al, 1991; Wang et al, 2011). These conflicting results underline the need for further investigation into the effects of morphine in the HIV-1-infected CNS.…”

Alcohol Enhances HIV Infection of Cord Blood Monocyte-Derived Macrophages

“…Total RNA (1 μg) was subjected to reverse transcription (Promega, Madison, WI). Real-time PCR was performed with the iQ SYBR Green Supermix (Bio-Rad Laboratories, Hercules, CA) as previously described [31, 32]. The oligonucleotide primers were synthesized by Integrated DNA Technologies, Inc. (Coralville, IA) and sequences will be available upon request.…”

Effects of addictive drugs on adult neural stem/progenitor cells

“…The effects of morphine and heroin on the inhibition of neuron-preferential differentiation were also indirectly proven in SH-SY5Y cells. miR-125b, which increases the differentiation of SH-SY5Y cells with neurite outgrowth [80], is significantly down-regulated by opioids such as morphine and heroin both in vitro and in vivo and is up-regulated during neuronal differentiation [81]. The δ-opioid peptide [ d -Ala 2 , d -Leu 5 ]-Enkephalin (DADLE) shows an anti-proliferative effect, which is derived from its regulation of the cell cycle by causing an arrest of AF5 cell cycle progression at the Gap 1 (G1) checkpoint [82].…”