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.
INTRODUCTION: We used proteomic analyses to assess how drug abuse modulates immunologic responses to infections with the humanimmunodeficiency 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: Chava B Pocernich; Debra Boyd-Kimball; H Fai Poon; Visith Thongboonkerd; Bert C Lynn; Jon B Klein; Vittorio Calebrese; Avindra Nath; D Allan Butterfield Journal: Brain Res Mol Brain Res Date: 2005-02-18
Authors: R L Shoeman; B Höner; T J Stoller; C Kesselmeier; M C Miedel; P Traub; M C Graves Journal: Proc Natl Acad Sci U S A Date: 1990-08 Impact factor: 11.205
Authors: J Snásel; R Shoeman; M Horejsí; O Hrusková-Heidingsfeldová; J Sedlácek; T Ruml; I Pichová Journal: Arch Biochem Biophys Date: 2000-05-15 Impact factor: 4.013
Authors: Edward R Cachay; Niousha Moini; Sergei L Kosakovsky Pond; Rick Pesano; Yolanda S Lie; Heidi Aiem; David M Butler; Scott Letendre; Wm Christopher Mathews; Davey M Smith Journal: Open AIDS J Date: 2007-10-22