Skip to main content

Advertisement

SpringerLink
Log in

Methamphetamine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells

  • Original Article
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Baselt RC (1982) Disposition of toxic drugs and chemicals in man, vol. 38. 2nd edn. Biomedical Publications, Davis, p 113

    Google Scholar 

  • Blauvelt A, Asada HM, Saville W, Klaus-Kovtun V, Altman DJ, Yarchoan R (1997) Productive infection of dendritic cells by HIV-1 and their ability to capture virus are mediated through separate pathways. J Clin Invest 100:2043–2053 doi:10.1172/JCI119737

    Article  PubMed  CAS  Google Scholar 

  • Cameron P, Pope M, Granelli-Piperno A, Steinman RM (1996) Dendritic cells and the replication of HIV-1. J Leukoc Biol 59:158–171

    PubMed  CAS  Google Scholar 

  • Cao H, Verge V, Baron C, Martinache C, Leon A, Scholl S (2000) In vitro generation of dendritic cells from human blood monocytes in experimental conditions compatible for in vivo cell therapy. J Hematother Stem Cell Res 9:183–194 doi:10.1089/152581600319397

    Article  PubMed  CAS  Google Scholar 

  • Caux C, Massacrier C, Vanbervliet B, Dubois B, Van Kooten C, Durand I (1994) Activation of human DC through CD40 cross-linking. J Exp Med 180:1263–1272 doi:10.1084/jem.180.4.1263

    Article  PubMed  CAS  Google Scholar 

  • Chackerian B, Long EM, Luciw PA, Overbaugh J (1997) Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection. J Virol 71:3932–3939

    PubMed  CAS  Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159 doi:10.1016/0003-2697(87)90021-2

    Article  PubMed  CAS  Google Scholar 

  • Coligan JE, Kruisbeek AM, Margulies DH, Shevach EM, Strober W (eds) (1991) In: Current protocols in immunology. Wiley, New York, pp 145–186 ISBN:0-471-52276-7

  • Dauer M, Obermaier B, Herten J, Haerle C, Pohl K, Rothenfusser S (2003) Mature dendritic cells derived from human monocytes within 48 hours: a novel strategy for dendritic cell differentiation from blood precursors. J Immunol 170:4069–4076

    PubMed  CAS  Google Scholar 

  • Gavrilin MA, Mathes IE, Podell M (2002) Methamphetamine enhances cell-associated feline immunodeficiency virus replication in astrocytes. J Neurovirol 8:240–249 doi:10.1080/13550280290049660

    Article  PubMed  CAS  Google Scholar 

  • Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR, Figdor CG, van Kooyk Y (2000) DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 100:587–597 doi:10.1016/S0092-8674(00)80694-7

    Article  PubMed  CAS  Google Scholar 

  • Granelli-Piperno A, Moser B, Pope M, Chen D, Wei Y, Isdell F (1996) Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors. J Exp Med 184:2433–2438 doi:10.1084/jem.184.6.2433

    Article  PubMed  CAS  Google Scholar 

  • Iritani BJ, Hallfors DD, Bauer DJ (2007) Crystal methamphetamine use among young adults in the USA. Addiction 102:1102–1113 doi:10.1111/j.1360-0443.2007.01847.x

    Article  PubMed  Google Scholar 

  • Jacque JM, Mann A, Enslen H, Sharova N, Brichacek B, Davis RJ (1998) Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase. EMBO J 17:2607–2618 doi:10.1093/emboj/17.9.2607

    Article  PubMed  CAS  Google Scholar 

  • Langhoff E, Terwilliger EF, Bos HJ, Kalland KH, Poznansky MC, Bacon OML (1991) Replication of human immunodeficiency virus type 1 in primary dendritic cell cultures. Proc Natl Acad Sci U S A 88:7998–8002 doi:10.1073/pnas.88.18.7998

    Article  PubMed  CAS  Google Scholar 

  • Larsen KE, Fon EA, Hastings TG, Edwards RH, Sulzer D (2002) Methamphetamine-induced degeneration of dopaminergic neurons involves autophagy and upregulation of dopamine synthesis. J Neurosci 22:8951–8960

    PubMed  CAS  Google Scholar 

  • Macatonia SE, Patterson S, Knight SC (1989) Suppression of immune responses by dendritic cells infected with HIV. Immunology 67:285–289

    PubMed  CAS  Google Scholar 

  • Munzar P, Goldberg SR (2000) Dopaminergic involvement in the discriminative-stimulus effects of methamphetamine in rats. Psychopharmacology (Berl) 148:209–216 doi:10.1007/s002130050044

    Article  CAS  Google Scholar 

  • Nair MP, Mahajan SD, Schwartz SA, Reynolds J, Whitney R, Bernstein Z (2005) Cocaine modulates dendritic cell-specific C type intercellular adhesion molecule-3-grabbing nonintegrin expression by dendritic cells in HIV-1 patients. J Immunol 174:6617–6626

    PubMed  CAS  Google Scholar 

  • National Drug Threat Assessment (NDTA) (2005) Summary report 2005. Methamphetamine. www.usdoj.gov/ndic/pubs11/13846/meth.htm

  • National Drug Threat Assessment (NDTA) (2007) Methamphetamine. http://www.usdoj.gov/ndic/pubs25/25921/meth.htm#Top

  • National Survey on Drug Use and Health (NSDUH) (2003) https://nsduhweb.rti.org

  • NIDA (National Institute of Drug abuse) INFO FACTS (2005) Methamphetamine. National Institute of Drug Abuse, Baltimore, May 2005

  • Office of National Drug Control Policy (ONDCP) (2007) Drug facts, methamphetamine. http://www.whitehousedrugpolicy.gov/drugfact/methamphetamine/index.html#go3

  • Pope M, Betjes MGH, Romani N, Cameron PU, Hoffman L, Gezelter S (1994) Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 78:389–398 doi:10.1016/0092-8674(94)90418-9

    Article  PubMed  CAS  Google Scholar 

  • Popik W, Hesselgesser E, Pitha PM (1998) Binding of human immunodeficiency virus type 1 to CD4 and CXCR4 receptors differentially regulates expression of inflammatory genes and activates the MEK/ERK signaling pathway. J Virol 72:6406–6413

    PubMed  CAS  Google Scholar 

  • Schepers RJF, Oyler JM, Joseph RE, Cone EJ, Moolchan ET, Huestis MA (2003) Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers. Clin Chem 49:121–132 doi:10.1373/49.1.121

    Article  PubMed  CAS  Google Scholar 

  • Shively L, Chang L, LeBon JM, Liu Q, Riggs AD, Singer-Sam J (2003) Real-time PCR assay for quantitative mismatch detection. Biotechniques 34:498–502

    PubMed  CAS  Google Scholar 

  • Takayasu T, Ohshima T, Nishigami J, Kondo T, Nagaon T (1995) Screening and determination of methamphetamine and amphetamine in the blood, urine and stomach contents in emergency medical care and autopsy cases. J Clin Forensic Med 2:25–33 doi:10.1016/1353-1131(95)90036-5

    Article  PubMed  CAS  Google Scholar 

  • Watanabe H, Sekihara S, Nomura Y (1989) Effect of dopamine receptor antagonist on in vivo dopamine release induced by intrastriatal perfusion with methamphetamine in freely moving rats. Methods Find Exp Clin Pharmacol 11:81–85

    PubMed  CAS  Google Scholar 

  • Weissman D, Li Y, Orenstein JM, Fauci AS (1995) Both a precursor and a mature population of dendritic cells can bind HIV. However, only the mature population that expresses CD80 can pass infection to unstimulated CD4+ T cells. J Immunol 155:4111–4117

    PubMed  CAS  Google Scholar 

  • Yang X, Gabuzda D (1999) Regulation of human immunodeficiency virus type 1 infectivity by the ERK mitogen-activated protein kinase signaling pathway. J Virol 73:3460–3466

    PubMed  CAS  Google Scholar 

  • Zhou LJ, Tedder TF (1996) CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc Natl Acad Sci U S A 93:2588–2592 doi:10.1073/pnas.93.6.2588

    Article  PubMed  CAS  Google Scholar 

Download references

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.

Author information

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

Authors
  1. Madhavan P. N. Nair
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zainulabedin M. Saiyed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Narayanan Nair
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nimisha H. Gandhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jose W. Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nawal Boukli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elias Provencio-Vasquez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Robert M. Malow
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maria Jose Miguez-Burbano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Madhavan P. N. Nair.

Additional information

Guarantor: Prof. Madhavan Nair

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

Keywords

Search

Navigation