Modulation of the proteome of peripheral blood mononuclear cells from HIV-1-infected patients by drugs of abuse.

Abstract

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.

• Authors: Jessica L Reynolds, Supriya D Mahajan, Ravikunar Aalinkeel, Bindukumar Nair, Donald E Sykes, Anardi Agosto-Mujica, Chiu Bin Hsiao, Stanley A Schwartz
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 29 Issue 5 Pg. 646-56 (Sep 2009) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 19543960 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Proteome
• Methamphetamine
• Cocaine

Topics

• Cells, Cultured
• Chromatography, High Pressure Liquid
• Cocaine (pharmacology)
• Electrophoresis, Gel, Two-Dimensional
• Gene Expression Regulation
• HIV Infections (blood, genetics, immunology, metabolism, pathology)
• HIV-1 (immunology, pathogenicity)
• Humans
• Leukocytes, Mononuclear (drug effects, metabolism, pathology, virology)
• Methamphetamine (pharmacology)
• Polymerase Chain Reaction
• Proteome (genetics, immunology, metabolism)
• Substance-Related Disorders (immunology)