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.
Clin Proteomics. 2012 Sep 7;9(1):11. doi: 10.1186/1559-0275-9-11.
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.
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.
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.
HIV 和 HCV 合并感染患者肝损伤的发病机制复杂且多因素。尽管人们对 HIV-1/HCV 合并感染的认识在全球范围内不断提高，但对于介导合并感染者快速进展为肝病的病理生理学机制知之甚少。
在这项研究中，我们研究了 HIV-1 单感染、HCV 单感染和 HIV-1/HCV 合并感染患者外周血单个核细胞的蛋白质组谱。高分辨率 2D 凝胶电泳和 PD quest 软件定量分析的结果表明，HIV-1、HCV 和 HIV-1/HCV 合并感染中几种蛋白质表达存在差异。液相色谱-质谱联用和 Mascot 数据库匹配（LC-MS/MS 分析）成功鉴定了 29 个独特的差异表达蛋白。这些蛋白包括细胞骨架蛋白（原肌球蛋白、凝胶蛋白、DYPLSL3、DYPLSL4 和前肌球蛋白-1）、伴侣蛋白和共伴侣蛋白（HSP90-β 和应激诱导磷酸蛋白）、代谢和凋亡前蛋白（鸟苷三磷酸[GTP]结合核蛋白 Ran、解毒酶谷胱甘肽 S-转移酶（GST）和 Rho GDP 解离抑制剂（Rho-GDI）、参与细胞生存机制的蛋白和参与基质合成的蛋白（胶原结合蛋白 2 [CBP2]）。在一组 HIV-1 单感染和合并感染患者（n=20）中，进一步验证了这 6 种最重要和最相关的蛋白在转录水平上的表达情况。
本研究揭示的特定促凋亡和抗凋亡蛋白特征有助于理解 HIV-1 和 HCV 合并感染中凋亡和保护性免疫介导的机制及其对合并感染者肝病进展的影响。
