Human Immunodeficiency Virus (HIV) Infection of Human Macrophages Is Increased by Dopamine: A Bridge between HIV-Associated Neurologic Disorders and Drug Abuse

• Published in: The American journal of pathology Vol. 175; no. 3; pp. 1148 - 1159
• Main Authors: Gaskill, Peter J, Calderon, Tina M, Luers, Aimee J, Eugenin, Eliseo A, Javitch, Jonathan A, Berman, Joan W
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.09.2009; American Society for Investigative Pathology
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Biological and medical sciences; Cells, Cultured; Central Nervous System - metabolism; Dopamine - metabolism; Dopamine - pharmacology; Dopamine Agents - metabolism; Dopamine Agents - pharmacology; Drug addiction; HIV - drug effects; HIV - physiology; HIV Infections - etiology; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - virology; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Investigative techniques, diagnostic techniques (general aspects); Macrophage Activation; Macrophages - metabolism; Macrophages - virology; Medical sciences; Mitogen-Activated Protein Kinase 3 - metabolism; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Phosphorylation; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Receptors, Dopamine D1 - agonists; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - metabolism; Regular; Signal Transduction; Substance-Related Disorders - complications; Substance-Related Disorders - metabolism; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virus Replication - drug effects; Human; Immunopathology; Drug addiction; Dopamine; Retroviridae; AIDS; Substance abuse; Catecholamine; Immune deficiency; Lentivirus; Infection; Virus; Bridges; Anatomic pathology; Addiction; Viral disease; Neurotransmitter; Complication; Human immunodeficiency virus; Macrophage
• ISSN: 0002-9440; 1525-2191
• DOI: 10.2353/ajpath.2009.081067

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.