Methamphetamine enhances HIV-1 infectivity in monocyte derived dendritic cells.
ABSTRACT The US is currently experiencing an epidemic of methamphetamine (Meth) use as a recreational drug. Recent studies also show a high prevalence of HIV-1 infection among Meth users. We report that Meth enhances HIV-1 infectivity of dendritic cells as measured by multinuclear activation of a galactosidase indicator (MAGI) cell assay, p24 assay, and LTR-RU5 amplification. Meth induces increased HIV-1 infection in association with an increase in the HIV-1 coreceptors, CXCR4 and CCR5, and infection is mediated by downregulation of extracellular-regulated kinase (ERK2) and the upregulation of p38 mitogen-activated protein kinase (MAPK). A p38 inhibitor (SB203580) specifically reversed the Meth-induced upregulation of the CCR5 HIV-1 coreceptor. The dopamine D2 receptor antagonist RS +/- sulpiride significantly reversed the Meth-induced upregulation of CCR5, demonstrating that the Meth-induced effect is mediated via the D2 receptor. These studies report for the first time that Meth fosters HIV-1 infection, potentially via upregulating coreceptor gene expression. Further, Meth mediates its regulatory effects via dopamine receptors and via downregulating ERK2 with a reciprocal upregulation of p38 MAPK. Elucidation of the role of Meth in HIV-1 disease susceptibility and the mechanism through which Meth mediates its effects on HIV-1 infection may help to devise novel therapeutic strategies against HIV-1 infection in high-risk Meth-using HIV-1-infected subjects.
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ABSTRACT: The reason co-morbid methamphetamine use and HIV infection lead to more rapid progression to AIDS is unclear. We used a model of methamphetamine self-administration to measure the effect of methamphetamine on the systemic immune system to better understand the co-morbidity of methamphetamine and HIV. Catheters were implanted into the jugular veins of male, Sprague Dawley rats so they could self-administer methamphetamine (n=18) or be given saline (control; n=16) for 14 days. One day after the last self-administration session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γ and TNF-α, and frequencies of CD4(+), CD8(+), CD200(+) and CD11b/c(+) lymphocytes in the spleen. Rats that self-administer methamphetamine had a lower frequency of CD4(+) T cells, but more of these cells produced IFN-γ. Methamphetamine did not alter the frequency of TNF-α-producing CD4(+) T cells. Methamphetamine using rats had a higher frequency of CD8(+) T cells, but fewer of them produced TNF-α. CD11b/c and CD200 expression were unchanged. Serum cytokine levels of IFN-γ, TNF-α and IL-6 in methamphetamine rats were unchanged. Methamphetamine lifetime dose inversely correlated with serum TNF-α levels. Or data suggest that methamphetamine abuse may exacerbate HIV disease progression by activating CD4 T cells, making them more susceptible to HIV infection, and contributing to their premature demise. Methamphetamine may also increase susceptibility to HIV infection, explaining why African American men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection. Copyright © 2015. Published by Elsevier B.V.European Journal of Pharmacology 02/2015; 752. DOI:10.1016/j.ejphar.2015.02.002 · 2.68 Impact Factor
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ABSTRACT: Background: Persons living with HIV (PLWH) who also use crack cocaine may have stressful, chaotic lives and typically do not engage in standard medical care that addresses a multitude of extenuating life circumstances. Yoga/meditation (YM) improves quality of life (QOL) and biomarkers of stress, but the effect of this intervention is almost unknown in PLWH, particularly those who use crack cocaine. Objectives: This pilot study sought to compare the feasibility and acceptability of 60-minute, twice-per-week sessions of YM for 2 months with those of no-contact control and to evaluate the effects of the intervention on QOL (according to the Short Form-36, Perceived Stress Scale [PSS], and Impact of Events Scale [IES]) and salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S) among PLWH who use crack cocaine. Design: Participants were randomly assigned to YM or no-contact control and were assessed at baseline, 2 months after the intervention, and 4 months' follow-up. Results: The YM program was acceptable and feasible, with high overall attendance (89%) and individual participation in yoga sessions (83%). YM participants showed modest improvements on QOL. The PSS total score and the IES intrusion score improved significantly 2 months after the intervention, but cortisol and DHEA-S did not change. Conclusions: This pilot study showed a high level of feasibility and acceptability and modest effects on measures of QOL among PLWH who use crack cocaine. The results suggest utility of YM as a simple, safe, and inexpensive format to improve QOL in a population that has many medical difficulties and extenuating stressors.Journal of alternative and complementary medicine (New York, N.Y.) 02/2015; 21(3). DOI:10.1089/acm.2014.0112 · 1.52 Impact Factor
Frontiers in Microbiology 03/2015; 6:217. DOI:10.3389/fmicb.2015.00217 · 3.94 Impact Factor