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 Eugenin, Jonathan A. Javitch, Joan W. Berman

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1148-1159
Number of pages12
JournalAmerican Journal of Pathology
Volume175
Issue number3
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Fingerprint

Virus Diseases
Nervous System Diseases
Substance-Related Disorders
Dopamine
Macrophages
HIV
Street Drugs
Virus Replication
Central Nervous System
Dopamine Receptors
Methamphetamine
Drug Users
Cocaine
Neurotransmitter Agents

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Human immunodeficiency virus (HIV) infection of human macrophages is increased by dopamine : A bridge between HIV-associated neurologic disorders and drug abuse. / Gaskill, Peter J.; Calderon, Tina M.; Luers, Aimée J.; Eugenin, Eliseo; Javitch, Jonathan A.; Berman, Joan W.

In: American Journal of Pathology, Vol. 175, No. 3, 01.01.2009, p. 1148-1159.

Research output: Contribution to journalArticle

Gaskill, Peter J. ; Calderon, Tina M. ; Luers, Aimée J. ; Eugenin, Eliseo ; Javitch, Jonathan A. ; Berman, Joan W. / Human immunodeficiency virus (HIV) infection of human macrophages is increased by dopamine : A bridge between HIV-associated neurologic disorders and drug abuse. In: American Journal of Pathology. 2009 ; Vol. 175, No. 3. pp. 1148-1159.
@article{f3b97db1cce84520bd5c6fa9b00067ee,
title = "Human immunodeficiency virus (HIV) infection of human macrophages is increased by dopamine: A bridge between HIV-associated neurologic disorders and drug abuse",
abstract = "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.",
author = "Gaskill, {Peter J.} and Calderon, {Tina M.} and Luers, {Aim{\'e}e J.} and Eliseo Eugenin and Javitch, {Jonathan A.} and Berman, {Joan W.}",
year = "2009",
month = "1",
day = "1",
doi = "10.2353/ajpath.2009.081067",
language = "English (US)",
volume = "175",
pages = "1148--1159",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Human immunodeficiency virus (HIV) infection of human macrophages is increased by dopamine

T2 - A bridge between HIV-associated neurologic disorders and drug abuse

AU - Gaskill, Peter J.

AU - Calderon, Tina M.

AU - Luers, Aimée J.

AU - Eugenin, Eliseo

AU - Javitch, Jonathan A.

AU - Berman, Joan W.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=70349237001&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349237001&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2009.081067

DO - 10.2353/ajpath.2009.081067

M3 - Article

C2 - 19661443

AN - SCOPUS:70349237001

VL - 175

SP - 1148

EP - 1159

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -