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

被引:24
作者
Nawal M Boukli
Vivekananda Shetty
Luis Cubano
Martha Ricaurte
Jordana Coelho-dos-Reis
Zacharie Nickens
Punit Shah
Andrew H Talal
Ramila Philip
Pooja Jain
机构
[1] Department of Microbiology and Immunology, School of Medicine Biomedical Proteomics Facility, Universidad Central del Caribe, Bayamon
[2] Immunotope, Inc., Pennsylvania Biotechnology Center, Doylestown, PA
[3] Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology Research, Drexel University, Doylestown, PA
[4] Center for Study of Hepatitis C, Weill Cornell Medical College, New York, NY
基金
美国国家卫生研究院;
关键词
2D-GE; HCV; HIV-1; HIV-1/HCV; Mass spectrometry; Pro-and anti-apoptotic fingerprinting; Proteomics;
D O I
10.1186/1559-0275-9-11
中图分类号
学科分类号
摘要
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 coinfection. 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. © 2012 Boukli et al.; licensee BioMed Central Ltd; licensee BioMed Central Ltd.
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