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Human immunodeficiency virus (HIV) infection of human macrophages is increased by dopamine: a bridge between HIV-associated neurologic disorders and drug abuse
Journal article   Open access   Peer reviewed

Human immunodeficiency virus (HIV) infection of human macrophages is increased by dopamine: a bridge between HIV-associated neurologic disorders and drug abuse

Peter J Gaskill, Tina M Calderon, Aimée J Luers, Eliseo A Eugenin, Jonathan A Javitch and Joan W Berman
The American journal of pathology, v 175(3), pp 1148-1159
Sep 2009
DOI: https://doi.org/10.2353/ajpath.2009.081067
PMID: 19661443
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
http://ajp.amjpathol.org/article/S0002944010606244/pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.2353/ajpath.2009.081067View
Published, Version of Record (VoR) Open

Abstract

Cells, Cultured Central Nervous System - metabolism Dopamine - metabolism Dopamine - pharmacology Dopamine Agents - metabolism Dopamine Agents - pharmacology HIV - drug effects HIV - physiology HIV Infections - etiology HIV Infections - immunology HIV Infections - metabolism HIV Infections - virology Humans Macrophage Activation Macrophages - metabolism Macrophages - virology Mitogen-Activated Protein Kinase 3 - metabolism Phosphorylation Receptors, Dopamine D1 - agonists Receptors, Dopamine D1 - metabolism Receptors, Dopamine D2 - agonists Receptors, Dopamine D2 - metabolism Signal Transduction Substance-Related Disorders - complications Substance-Related Disorders - metabolism Virus Replication - drug effects
The prevalence of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) that result from HIV infection of the central nervous system is increasing. Macrophages, the primary target for HIV within the central nervous system, play a central role in HIV-induced neuropathogenesis. Drug abuse exacerbates HAND, but the mechanism(s) by which this increased neuropathology results in more severe forms of HAND in HIV-infected drug abusers is unclear. The addictive and reinforcing effects of many drugs of abuse, such as cocaine and methamphetamine, are mediated by increased extracellular dopamine in the brain. We propose a novel mechanism by which drugs of abuse intensify HIV neuropathogenesis through direct effects of the neurotransmitter dopamine on HIV infection of macrophages. We found that macrophages express dopamine receptors 1 and 2, and dopamine activates macrophages by increasing ERK 1 phosphorylation. Our results demonstrate for the first time that dopamine increases HIV replication in human macrophages and that the mechanism by which dopamine mediates this change is by increasing the total number of HIV-infected macrophages. This increase in HIV replication is mediated by activation of dopamine receptor 2. These findings suggest a common mechanism by which drugs of abuse enhance HIV replication in macrophages and indicate that the drug abuse-heightened levels of central nervous system dopamine could increase viral replication, thereby accelerating the development of HAND.

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Collaboration types
Domestic collaboration
Web of Science research areas
Pathology
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