Modulation of the Proteome of Peripheral Blood Mononuclear Cells from HIV-1-Infected Patients by Drugs of Abuse

• Published in: Journal of clinical immunology 2009-09, Vol.29 (5), p.646-656
• Main Authors: Reynolds, Jessica L, Mahajan, Supriya D, Aalinkeel, Ravikunar, Nair, Bindukumar, Sykes, Donald E, Agosto-Mujica, Anardi, Hsiao, Chiu Bin, Schwartz, Stanley A
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Chromatography, High Pressure Liquid; Cocaine; Cocaine - pharmacology; Data processing; Drug abuse; Electrophoresis, Gel, Two-Dimensional; Gel electrophoresis; Gene expression; Gene Expression Regulation; HIV Infections - blood; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - pathology; HIV-1 - immunology; HIV-1 - pathogenicity; Human immunodeficiency virus 1; Humans; Immunology; Infection; Infectious Diseases; Internal Medicine; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Leukocytes, Mononuclear - virology; Lymphocytes B; Lymphocytes T; Medical Microbiology; Methamphetamine; Methamphetamine - pharmacology; Molecular modelling; Monocytes; Peripheral blood mononuclear cells; Polymerase Chain Reaction; Proteome - genetics; Proteome - immunology; Proteome - metabolism; proteomics; Substance-Related Disorders - immunology
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-009-9309-5

Introduction 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.