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

Nawal M Boukli,Andrew H Talal,Ramila Philip,Pooja Jain,Martha Ricaurte,Jordana Coelho-Dos-Reis,Punit Shah,Luis Cubano,Zacharie Nickens,Vivekananda Shetty

doi:10.1186/1559-0275-9-11

Abstract

BackgroundPathogenesis 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.ResultsIn 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.ConclusionsThe 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.

Highlights

Pathogenesis of liver damage in patients with HIV and Hepatitis C virus (HCV) co-infection is complex and multifactorial
While a few proteomics studies have focused on the analysis of serum samples from human immunodeficiency virus type 1 (HIV-1), HCV mono- and co-infected patients, the proteomic analysis of peripheral blood mononuclear cells (PBMCs) has seldom been reported for these patients, which are highly relevant in the context of HIV-1/HCV co-infection
HIV-1, HCV, and HIV-1/HCV co-infected PBMC proteome To facilitate quantitative detection and to maximize identification of changes in the proteome induced by HIV-1, HCV, and HIV-1/HCV PBMCs, cell lysates were subjected to a 2D gel electrophoresis coupled with LC-MS/MS mass spectrometry analysis

Summary

Introduction

Pathogenesis of liver damage in patients with HIV and HCV co-infection is complex and multifactorial. Different studies have shown the presence of low levels of HCV RNA in serum and lymphoid cells after spontaneous or Interferon/Ribavirin-induced resolution of chronic hepatitis C [17,18]. It was demonstrated that HCV might persist and replicate in the liver and PBMC of healthy, anti-HCV antibody-positive, serum HCV RNA-negative patients who have persistently normal ALT levels [19]. This could present a potential risk for transmission and reactivation especially in the presence of HIV. It is critical to understand the influence of both these viruses on peri-pheral lymphoid cells

Methods

Results

Conclusion