Top

Published in:

01-09-2009

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

Authors: Jessica L. Reynolds, Supriya D. Mahajan, Ravikunar Aalinkeel, Bindukumar Nair, Donald E. Sykes, Anardi Agosto-Mujica, Chiu Bin Hsiao, Stanley A. Schwartz

Published in: Journal of Clinical Immunology | Issue 5/2009

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.

Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report 2006 (www.avert.org/statsum.htm)

Nath A, Maragos WF, Avison MJ, Schmitt FA, Berger JR. Acceleration of HIV dementia with methamphetamine and cocaine. J Neurovirol. 2001;7(1):66–71.PubMedCrossRef

Mohri H, Markowitz Me. In vitro characterization of multidrug-resistant HIV-1 isolates from a recently infected patient associated with dual tropism and rapid disease progression. J Acquir Immune Defic Syndr. 2008;48(5):511–21.PubMedCrossRef

Duncan R, Shapshak P, Page JB, Chiappelli F, McCoy CB, Messiah SE. Crack cocaine: effect modifier of RNA viral load and CD4 count in HIV infected African American women. Front Biosci. 2007;12:1488–95.PubMedCrossRef

Cook JA, Burke-Miller JK, Cohen MH, Cook RL, Vlahov D, Wilson TE, et al. Crack cocaine, disease progression, and mortality in a multicenter cohort of HIV-1 positive women. AIDS. 2008;22(11):1355–63.PubMedCrossRef

Peterson PK, Gekker G, Schut R, Hu S, Balfour HH Jr, Chao CC. Enhancement of HIV-1 replication by opiates and cocaine: the cytokine connection. Adv Exp Med Biol. 1993;335:181–8.PubMed

Peterson PK, Gekker G, Chao CC, Schut R, Molitor TW, Balfour HH Jr. Cocaine potentiates HIV-1 replication in human peripheral blood mononuclear cell cocultures. Involvement of transforming growth factor-beta. J Immunol. 1991;146(1):81–4.PubMed

Nair MP, Mahajan SD, Schwartz SA, Reynolds J, Whitney R, Bernstein Z, et al. Cocaine modulates dendritic cell-specific C type intercellular adhesion molecule-3-grabbing nonintegrin expression by dendritic cells in HIV-1 patients. J Immunol. 2005;174(11):6617–26.PubMed

Reynolds JL, Mahajan SD, Sykes DE, Schwartz SA. Nair MP Proteomic analyses of methamphetamine (METH)-induced differential protein expression by immature dendritic cells (IDC). Biochim Biophys Acta. 2007;1774(4):433–42.PubMed

10.

Liang H, Wang X, Chen H, Song L, Ye L, Wang SH, et al. Methamphetamine enhances HIV infection of macrophages. Am J Pathol. 2008;172(6):1617–24.PubMedCrossRef

11.

Ellis RJ, Childers ME, Cherner M, Lazzaretto D, Letendre S, Grant I. Increased human immunodeficiency virus loads in active methamphetamine users are explained by reduced effectiveness of antiretroviral therapy. J Infect Dis. 2003;188:1820–6.PubMedCrossRef

12.

Cachay ER, Moini N, Kosakovsky Pond SL, Pesano R, Lie YS, Aiem H, et al. Active methamphetamine use is associated with transmitted drug resistance to non-nucleoside reverse transcriptase inhibitors in individuals with HIV infection of unknown duration. Open AIDS J. 2007;1:5–10.PubMed

13.

Lee YW, Hennig B, Yao J, Toborek M. Methamphetamine induces AP-1 and NF-kappaB binding and transactivation in human brain endothelial cells. J Neurosci Res. 2001;66:583–91.PubMedCrossRef

14.

Tallóczy Z, Martinez J, Joset D, Ray Y, Gácser A, Toussi S, et al. Methamphetamine inhibits antigen processing, presentation, and phagocytosis. PLoS Pathog. 2008;4(2):e28.PubMedCrossRef

15.

Edwards DJ, Bowles SK. Protein binding of cocaine in human serum. Pharm Res. 1988;5:440–2.PubMedCrossRef

16.

Takayasu T, Ohshima T, Nishigami J, Kondo T, Nagaon T. Screening and determination of methamphetamine and amphetamine in the blood, urine and stomach contents in emergency medical care and autopsy cases. J Clin Forensic Med. 1995;2:25–33.PubMedCrossRef

17.

Kalasinsky KS, Bosy TZ, Schmunk GA, Reiber G, Anthony RM, Furukawa Y, et al. Regional distribution of methamphetamine in autopsied brain of chronic human methamphetamine users. Forensic Sci Int. 2001;116:163–9.PubMedCrossRef

18.

Schepers RJF, Oyler JM, Joseph RE, Cone EJ, Moolchan ET, Huestis MA. Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers. Clin Chem. 2003;49:121–32.PubMedCrossRef

19.

Wessel D, Flügge UI. A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal Biochem. 1984;138(1):141–3.PubMedCrossRef

20.

Breci L, Hattrup E, Keeler M, Letarte J, Johnson R, Haynes PA. Comprehensive proteomics in yeast using chromatographic fractionation, gas phase fractionation, protein gel electrophoresis, and isoelectric focusing. Proteomics. 2005;5(8):2018–28.PubMedCrossRef

21.

Gharahdaghi F, Weinberg CR, Meagher DA, Imai BS, Mische SM. Mass spectrometric identification of proteins from silver-stained polyacrylamide gel: a method for the removal of silver ions to enhance sensitivity. Electrophoresis. 1999;20(3):601–5.PubMedCrossRef

22.

Cooper B, Eckert D, Andon NL, Yates JR, Haynes PA. Investigative proteomics: identification of an unknown plant virus from infected plants using mass spectrometry. J Am Soc Mass Spectrom. 2003;14(7):736–41.PubMedCrossRef

23.

Wilm M, Shevchenko A, Houthaeve T, Breit S, Schweigerer L, Fotsis T, et al. Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry. Nature. 1996;379(6564):466–9.PubMedCrossRef

24.

Haynes PA, Gygi SP, Figeys D, Aebersold R. Proteome analysis: biological assay or data archive? Electrophoresis. 1998;19(11):1862–71.PubMedCrossRef

25.

Andon NL, Hollingworth S, Koller A, Greenland AJ, Yates JR 3rd, Haynes PA. Proteomic characterization of wheat amyloplasts using identification of proteins by tandem mass spectrometry. Proteomics. 2002;2(9):1156–68.PubMedCrossRef

26.

Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem. 1987;162(1):156–9.PubMedCrossRef

27.

Shively L, Chang L, LeBon JM, Liu Q, Riggs AD, Singer-Sam J. Real-time PCR assay for quantitative mismatch detection. Biotechniques. 2003;34:498–502.PubMed

28.

Prohászka Z, Füst G. Immunological aspects of heat-shock proteins—the optimum stress of life. Mol Immunol. 2004;41(1):29–44.PubMedCrossRef

29.

Gullo CA, Teoh G. Heat shock proteins: to present or not, that is the question. Immunol Lett. 2004;94(1-2):1–10.PubMedCrossRef

30.

Wainberg Z, Oliveira M, Lerner S, Tao Y, Brenner BG. Modulation of stress protein (hsp27 and hsp70) expression in CD4+ lymphocytic cells following acute infection with human immunodeficiency virus type-1. Virology. 1997;233:364–73.PubMedCrossRef

31.

Gurer C, Cimarelli A, Luban J. Specific incorporation of heat shock protein 70 family members into primate lentiviral virions. J Virol. 2002;76:4666–70.PubMedCrossRef

32.

Agostini I, Popov S, Li J, Dubrovsky L, Hao T, Bukrinsky M. Heat-shock protein 70 can replace viral protein R of HIV-1 during nuclear import of the viral preintegration complex. Exp Cell Res. 2000;259:398–403.PubMedCrossRef

33.

Iordanskiy S, Zhao Y, Dubrovsky L, Iordanskaya T, Chen M, Liang D, et al. Heat shock protein 70 protects cells from cell cycle arrest and apoptosis induced by human immunodeficiency virus type 1 viral protein R. J Virol. 2004;78:9697–704.PubMedCrossRef

34.

Iordanskiy S, Zhao Y, DiMarzio P, Agostini I, Dubrovsky L, Bukrinsky M. Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr-independent HIV-1 replication in macrophages. Blood. 2004;104:1867–72.PubMedCrossRef

35.

Wang N, Stamenovic D. Mechanics of vimentin intermediate filaments. J Muscle Res Cell Motil. 2002;23(5–6):535–40.PubMedCrossRef

36.

Snásel J, Shoeman R, Horejsí M, Hrusková-Heidingsfeldová O, Sedlácek J, Ruml T, et al. Cleavage of vimentin by different retroviral proteases. Arch Biochem Biophys. 2000;377(2):241–5.PubMedCrossRef

37.

Höner B, Shoeman RL, Traub P. Human immunodeficiency virus type 1 protease microinjected into cultured human skin fibroblasts cleaves vimentin and affects cytoskeletal and nuclear architecture. J Cell Sci. 1991;100(Pt 4):799–807.PubMed

38.

Höner B, Shoeman RL, Traub P. Degradation of cytoskeletal proteins by the human immunodeficiency virus type 1 protease. Cell Biol Int Rep. 1992;16(7):603–12.PubMedCrossRef

39.

Shoeman RL, Höner B, Stoller TJ, Kesselmeier C, Miedel MC, Traub P, et al. Human immunodeficiency virus type 1 protease cleaves the intermediate filament proteins vimentin, desmin, and glial fibrillary acidic protein. Proc Natl Acad Sci U S A. 1990;87(16):6336–40.PubMedCrossRef

40.

Shoeman RL, Hüttermann C, Hartig R, Traub P. Amino-terminal polypeptides of vimentin are responsible for the changes in nuclear architecture associated with human immunodeficiency virus type 1 protease activity in tissue culture cells. Mol Biol Cell. 2001;12(1):143–54.PubMed

41.

Karczewski MK, Strebel K. Cytoskeleton association and virion incorporation of the human immunodeficiency virus type 1 Vif protein. J Virol. 1996;70(1):494–507.PubMed

42.

Henzler T, Harmache A, Herrmann H, Spring H, Suzan M, Audoly G, et al. Fully functional, naturally occurring and C-terminally truncated variant human immunodeficiency virus (HIV) Vif does not bind to HIV Gag but influences intermediate filament structure. J Gen Virol. 2001;82(Pt 3):561–73.PubMed

43.

Pocernich CB, Boyd-Kimball D, Poon HF, Thongboonkerd V, Lynn BC, Klein JB, et al. Proteomics analysis of human astrocytes expressing the HIV protein Tat. Brain Res Mol Brain Res. 2005;133(2):307–16.PubMedCrossRef

44.

Geiben-Lynn R, Kursar M, Brown NV, Addo MM, Shau H, Lieberman J, et al. HIV-1 antiviral activity of recombinant natural killer cell enhancing factors, NKEF-A and NKEF-B, members of the peroxiredoxin family. J Biol Chem. 2003;278(3):1569–74.PubMedCrossRef

45.

Ross EM. Coordinating speed and amplitude in G-protein signaling. Curr Biol. 2008;18(17):R777–83.PubMedCrossRef

46.

Stantchev TS, Broder CC. Human immunodeficiency virus type-1 and chemokines: beyond competition for common cellular receptors. Cytokine Growth Factor Rev. 2001;12(2–3):219–43.PubMedCrossRef

47.

Audoly G, Popoff MR, Gluschankof P. Involvement of a small GTP binding protein in HIV-1 release. Retrovirology. 2005;2:4.CrossRef

48.

Lin YL, Mettling C, Portalès P, Réant B, Clot J, Corbeau P. G-protein signaling triggered by R5 human immunodeficiency virus type 1 increases virus replication efficiency in primary T lymphocytes. J Virol. 2005;79(12):7938–41.PubMedCrossRef

49.

Ibeh BO, Obidoa O, Uzoegwu PN. High plasma activity of endogenous antioxidants protect CD4+ T-cells in HIV-serodiscordant heterosexual partners in a Nigerian population. Int J STD AIDS. 2008;19(8):536–40.PubMedCrossRef

50.

Agrawal L, Louboutin JP, Reyes BA, Van Bockstaele EJ, Strayer DS. Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis. Gene Ther. 2006;13(23):1645–56.PubMedCrossRef

51.

Elola MT, Wolfenstein-Todel C, Troncoso MF, Vasta GR, Rabinovich GA. Galectins: matricellular glycan-binding proteins linking cell adhesion, migration, and survival. Cell Mol Life Sci. 2007;64(13):1679–700.PubMedCrossRef

52.

Elola MT, Chiesa ME, Alberti AF, Mordoh J, Fink NE. Galectin-1 receptors in different cell types. J Biomed Sci. 2005;12(1):13–29.PubMedCrossRef

53.

Mercier S, St-Pierre C, Pelletier I, Ouellet M, Tremblay MJ, Sato S. Galectin-1 promotes HIV-1 infectivity in macrophages through stabilization of viral adsorption. Virology. 2008;371(1):121–9.PubMedCrossRef

54.

Ouellet M, Mercier S, Pelletier I, Bounou S, Roy J, Hirabayashi J, et al. Galectin-1 acts as a soluble host factor that promotes HIV-1 infectivity through stabilization of virus attachment to host cells. J Immunol. 2005;174(7):4120–6.PubMed

Title: Modulation of the Proteome of Peripheral Blood Mononuclear Cells from HIV-1-Infected Patients by Drugs of Abuse
Authors: Jessica L. Reynolds
Supriya D. Mahajan
Ravikunar Aalinkeel
Bindukumar Nair
Donald E. Sykes
Anardi Agosto-Mujica
Chiu Bin Hsiao
Stanley A. Schwartz
Publication date: 01-09-2009
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 5/2009
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-009-9309-5

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Introduction

Methods

Results

Please log in to get access to this content

Other articles of this Issue 5/2009

siRNA Knockdown of PD-L1 and PD-L2 in Monocyte-Derived Dendritic Cells only Modestly Improves Proliferative Responses to Gag by CD8+ T Cells from HIV-1-Infected Individuals

Increases in Serum TARC/CCL17 Levels Are Associated with Progression-Free Survival in Advanced Melanoma Patients in Response to Dendritic Cell-Based Immunotherapy

A Novel Mutation in a Patient with a Deficiency of the Eighth Component of Complement Associated with Recurrent Meningococcal Meningitis

Interleukin 18 Promoter Variants (−137G>C and −607C>A) in Patients with Chronic Hepatitis C: Association with Treatment Response

Clinico-immunologic Study on Immunotherapy with Mixed and Single Insect Allergens

Sequential Changes in Serum Cytokines Reflect Viral RNA Kinetics in Target Organs of a Coxsackievirus B Infection in Mice

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials