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

Clinical Proteomics

Martha Ricaurte²  Luis Cubano²  Nawal M Boukli²  Vivekananda Shetty¹  Pooja Jain⁴  Jordana Coelho-dos-Reis⁴  Ramila Philip¹  Andrew H Talal³  Punit Shah¹  Zacharie Nickens¹ 

[1] Immunotope, Inc., Pennsylvania Biotechnology Center, Doylestown, USAImmunotope, Inc., Pennsylvania Biotechnology Center, Doylestown, USAImmunotope, Inc., Pennsylvania Biotechnology Center, Doylestown, USA;Biomedical Proteomics Facility Department of Microbiology and Immunology, Universidad Central del Caribe School of Medicine, Bayamon, Puerto RicoBiomedical Proteomics Facility Department of Microbiology and Immunology, Universidad Central del Caribe School of Medicine, Bayamon, Puerto RicoBiomedical Proteomics Facility Department of Microbiology and Immunology, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico;Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, USACenter for the Study of Hepatitis C, Weill Cornell Medical College, New York, USACenter for the Study of Hepatitis C, Weill Cornell Medical College, New York, USA;Department of Microbiology and Immunology, and the Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Doylestown, USADepartment of Microbiology and Immunology, and the Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Doylestown, USADepartment of Microbiology and Immunology, and the Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Doylestown, USA

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

DOI  :  10.1186/1559-0275-9-11

来源: Humana Press Inc

【 摘 要 】

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 (n = 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.

【 授权许可】

Unknown