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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

https://doi.org/10.2353/ajpath.2009.081067Get rights and content

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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Supported by National Institutes of Mental Health grants MH083497 (to J.W.B.), MH05679 (to J.W.B. and T.M.C.), MH076679 (to E.A.E.), and MH054137 (to J.A.J); National Institutes of Drug Abuse grants F32DA024965 (to P.J.G.), DA025567 (to J.W.B. and T.M.C.), and DA022413 (to J.A.J); NIH Centers for AIDS research grant CFAR AI-051519, especially the Immunology/Pathology Core; and NIH experimental neuropathology training grant NS07098 (to P.J.G.).

A guest editor acted as editor-in-chief for this manuscript. No person at Thomas Jefferson University or Albert Einstein College of Medicine was involved in the peer review process or final disposition for this article.

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