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Methamphetamine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells

Journal of Neuroimmune Pharmacology volume 4, pages 129–139 (2009)Cite this article

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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Acknowledgements

This work was supported in part by the National Institute on Drug Abuse Grants RO1-DA012366, RO1-DA014218, RO1-DA015628, RO1-DA021537, and RO1AA017405.

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Authors and Affiliations

  1. Department of Immunology, College of Medicine, Florida International University, Miami, FL, 33155, USA

    Madhavan P. N. Nair, Zainulabedin M. Saiyed, Narayanan Nair & Nimisha H. Gandhi

  2. School of Medicine, Universidad Central del Caribe, Bayamon, 00960, Puerto Rico

    Jose W. Rodriguez & Nawal Boukli

  3. School of Nursing and Health Studies, University of Miami, Miami, FL, 33124, USA

    Elias Provencio-Vasquez

  4. College of Health and Urban Affairs, Stempel School of Public Health, Florida International University, Miami, FL, 33181, USA

    Robert M. Malow

  5. Department of Epidemiology and Public Health, Florida International University, Miami, FL, 33181, USA

    Maria Jose Miguez-Burbano

  6. Department of Immunology, College of Medicine, Florida International University, Miami Children’s Hospital, George E. Batchelor Research and Academic Pavilion, 3196 S.W. 62 Avenue, Miami, FL, 33155-3009, USA

    Madhavan P. N. Nair

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  1. Madhavan P. N. Nair
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  2. Zainulabedin M. Saiyed
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  9. Maria Jose Miguez-Burbano
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Correspondence to Madhavan P. N. Nair.

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Nair, M.P.N., Saiyed, Z.M., Nair, N. et al. Methamphetamine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells. J Neuroimmune Pharmacol 4, 129–139 (2009). https://doi.org/10.1007/s11481-008-9128-0

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  • DOI: https://doi.org/10.1007/s11481-008-9128-0

Keywords

  • dendritic cells
  • HIV-1 infectivity
  • MAGI assay
  • dopamine D2 receptor
  • p38 MAPK
  • chemokine receptors