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Unique and differential protein signatures within the mononuclear cells of HIV-1 and HCV mono-infected and co-infected patients

Nawal M Boukli1, Vivekananda Shetty2, Luis Cubano1, Martha Ricaurte1, Jordana Coelho-dos-Reis3, Zacharie Nickens2, Punit Shah2, Andrew H Talal4, Ramila Philip2 and Pooja Jain3*

Author Affiliations

1 Universidad Central del Caribe School of Medicine, Biomedical Proteomics Facility Department of Microbiology and Immunology, Bayamon, Puerto Rico

2 Immunotope, Inc., Pennsylvania Biotechnology Center, Doylestown, PA, USA

3 Department of Microbiology and Immunology, and the Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, 3805 Old Easton Road, Doylestown, PA, USA

4 Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, NY, USA

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Clinical Proteomics 2012, 9:11  doi:10.1186/1559-0275-9-11

Published: 7 September 2012

Abstract

Background

Pathogenesis of liver damage in patients with HIV and HCV co-infection is complex and multifactorial. Although global awareness regarding HIV-1/HCV co-infection is increasing little is known about the pathophysiology that mediates the rapid progression to hepatic disease in the co-infected individuals.

Results

In this study, we investigated the proteome profiles of peripheral blood mononuclear cells from HIV-1 mono-, HCV mono-, and HIV-1/HCV co-infected patients. The results of high-resolution 2D gel electrophoresis and PD quest software quantitative analysis revealed that several proteins were differentially expressed in HIV-1, HCV, and HIV-1/HCV co-infection. Liquid chromatography-mass spectrometry and Mascot database matching (LC-MS/MS analysis) successfully identified 29 unique and differentially expressed proteins. These included cytoskeletal proteins (tropomyosin, gelsolin, DYPLSL3, DYPLSL4 and profilin-1), chaperones and co-chaperones (HSP90-beta and stress-induced phosphoprotein), metabolic and pre-apoptotic proteins (guanosine triphosphate [GTP]-binding nuclear protein Ran, the detoxifying enzyme glutathione S-transferase (GST) and Rho GDP-dissociation inhibitor (Rho-GDI), proteins involved in cell prosurvival mechanism, and those involved in matrix synthesis (collagen binding protein 2 [CBP2]). The six most significant and relevant proteins were further validated in a group of mono- and co-infected patients (nā€‰=ā€‰20) at the transcriptional levels.

Conclusions

The specific pro- and anti- apoptotic protein signatures revealed in this study could facilitate the understanding of apoptotic and protective immune-mediated mechanisms underlying HIV-1 and HCV co-infection and their implications on liver disease progression in co-infected patients.

Keywords:
HIV-1; HCV; HIV-1/HCV; 2D-GE; Mass spectrometry; Pro- and anti-apoptotic fingerprinting; Proteomics