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Cocaine-mediated enhancement of virus replication in macrophages: Implications for human immunodeficiency virus-associated dementia

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Abstract

Injection drug use has been recognized as a major risk factor for acquired immunodeficiency syndrome (AIDS) from the outset of the epidemic. Cocaine, one of the most widely abused drugs in the United States, can both impair the functions of macrophages and CD4+ lymphocytes and also activate human immunodeficiency virus (HIV)-1 expression in these cells. Because the brain is the target organ for both cocaine and HIV, the objective of the present study was to explore the effects of cocaine on virus replication in macrophages, the target cells for the virus in the central nervous system (CNS). Cocaine markedly enhanced virus production in simian human immunodeficiency virus (SHIV)-infected monocyte-derived macrophages (MDMs) and in U1 cells, a chronically infected promonocytic cell line as monitored by enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry. Cocaine treatment also resulted in the activation of nuclear factor (NF)-κB and transcriptional activation of the HIV-LTR (long terminal repeat) gag-GFP (green fluorescent protein). Analyses of chemokines in cocaine-treated macrophages by real-time reverse transcriptase—polymerase chain reaction (RT-PCR) and Luminex assays suggested increased expression of interleukin (IL)-10, a cytokine that is known to promote HIV replication in MDMs. In addition to enhancing IL-10 expression, cocaine also caused an up-regulation of the macrophage activation marker, human leukocyte antigen (HLA)-DR, in MDMs. The synergistic effect of cocaine on virus replication and its enhancement of host activation markers suggest that cocaine functions at multiple pathways to accelerate HIV-associated dementia (HAD).

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Authors and Affiliations

  1. Department of Molecular and Integrative Physiology, 5000 Wahl Hall East, University of Kansas Medical Center, 3901 Rainbow Blvd, 66160, Kansas City, KS, USA

    Navneet K. Dhillon, Rachel Williams, Fuwang Peng, Yi-jou Tsai, Brandon Nicolay, Milind Gadgil & Shilpa J. Buch

  2. Department of Microbiology, Immunology and Molecular Genetics, University of Kansas Medical Center, Kansas City, Kansas, USA

    Sukhbir Dhillon

  3. University of Missouri Kansas City, Kansas, USA

    Anil Kumar

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  1. Navneet K. Dhillon
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  2. Rachel Williams
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  3. Fuwang Peng
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  4. Yi-jou Tsai
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  5. Sukhbir Dhillon
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  6. Brandon Nicolay
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  7. Milind Gadgil
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  8. Anil Kumar
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  9. Shilpa J. Buch
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Correspondence to Shilpa J. Buch.

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This work was supported by grants MH62969-01, RR016443, MH-068212, MH072355, and DA020392-01 from the National Institutes of Health.

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Dhillon, N.K., Williams, R., Peng, F. et al. Cocaine-mediated enhancement of virus replication in macrophages: Implications for human immunodeficiency virus-associated dementia. Journal of NeuroVirology 13, 483–495 (2007). https://doi.org/10.1080/13550280701528684

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  • DOI: https://doi.org/10.1080/13550280701528684

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