Modulation of the proteome of peripheral blood mononuclear cells from HIV-1-infected patients by drugs of abuse.
BACKGROUND
We used proteomic analyses to assess how drug abuse modulates immunologic responses to infections with the human immunodeficiency virus type 1 (HIV-1).


METHODS
Two-dimensional difference gel electrophoresis was utilized to determine changes in the proteome of peripheral blood mononuclear cells (PBMC) isolated from HIV-1-positive donors that occurred after treatment with cocaine or methamphetamine. Both drugs differentially regulated the expression of several functional classes of proteins. We further isolated specific subpopulations of PBMC to determine which subpopulations were selectively affected by treatment with drugs of abuse. Monocytes, B cells, and T cells were positively or negatively selected from PBMC isolated from HIV-1-positive donors.


RESULTS
Our results demonstrate that cocaine and methamphetamine modulate gene expression primarily in monocytes and T cells, the primary targets of HIV-1 infection. Proteomic data were validated with quantitative, real-time polymerase chain reaction. These studies elucidate the molecular mechanisms underlying the effects of drugs of abuse on HIV-1 infections. Several functionally relevant classes of proteins were identified as potential mediators of HIV-1 pathogenesis and disease progression associated with drug abuse.
Reynolds
Jessica L
JL
Department of Medicine, Division of Allergy, Immunology and Rheumatology, Buffalo General Hospital, University at Buffalo, State University of New York at Buffalo, 311 MultiLab Research Building, Buffalo, NY,14203, USA. jlr8@buffalo.edu
Mahajan
Supriya D
SD
Aalinkeel
Ravikunar
R
Nair
Bindukumar
B
Sykes
Donald E
DE
Agosto-Mujica
Anardi
A
Hsiao
Chiu Bin
CB
Schwartz
Stanley A
SA
D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008694:Methamphetamine / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D020543:Proteome / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000276:immunology
D020543:Proteome; D008694:Methamphetamine; D003042:Cocaine