Reynolds Jessica L, Mahajan Supriya D, Sykes Donald E, Schwartz Stanley A, Nair Madhavan P N
Department of Medicine, Division of Allergy, Immunology and Rheumatology, State University of New York at Buffalo, Buffalo General Hospital, Buffalo, NY 14203, USA.
Biochim Biophys Acta. 2007 Apr;1774(4):433-42. doi: 10.1016/j.bbapap.2007.02.001. Epub 2007 Feb 13.
In the US, the increase in methamphetamine (METH) use has been associated with increased human immunodeficiency virus (HIV-1) infection. Dendritic cells (DC) are the first line of defense against HIV-1. DC play a critical role in harboring HIV-1 and facilitate the infection of neighboring T cells. However, the role of METH on HIV-1 infectivity and the expression of the proteome of immature dendritic cells (IDC) has not been elucidated. We hypothesize that METH modulates the expression of a number of proteins by IDC that foster the immunopathogenesis of HIV-1 infection. We utilized LTR amplification, p24 antigen assay and the proteomic method of difference gel electrophoresis (DIGE) combined with protein identification through high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to analyze the effects of METH on HIV-1 infectivity (HIV-1 IIIB; CXCR4-tropic, X4 strain) and the proteomic profile of IDC. Our results demonstrate that METH potentiates HIV-1 replication in IDC. Furthermore, METH significantly differentially regulates the expression of several proteins including CXCR3, protein disulfide isomerase, procathepsin B, peroxiredoxin and galectin-1. Identification of unique, METH-induced proteins may help to develop novel markers for diagnostic, preventive and therapeutic targeting in METH using subjects.
在美国,甲基苯丙胺(METH)使用的增加与人类免疫缺陷病毒(HIV-1)感染率上升有关。树突状细胞(DC)是抵御HIV-1的第一道防线。DC在隐匿HIV-1并促进邻近T细胞感染方面发挥着关键作用。然而,METH对HIV-1感染性以及未成熟树突状细胞(IDC)蛋白质组表达的作用尚未阐明。我们假设METH会调节IDC中多种蛋白质的表达,这些蛋白质会促进HIV-1感染的免疫发病机制。我们利用长末端重复序列(LTR)扩增、p24抗原检测以及差异凝胶电泳(DIGE)蛋白质组学方法,并结合高效液相色谱-串联质谱(HPLC-MS/MS)进行蛋白质鉴定,来分析METH对HIV-1感染性(HIV-1 IIIB;趋化因子CXCR4型,X4毒株)以及IDC蛋白质组图谱的影响。我们的结果表明,METH会增强HIV-1在IDC中的复制。此外,METH会显著差异调节多种蛋白质的表达,包括CXCR3、蛋白二硫键异构酶、组织蛋白酶原B、过氧化物还原酶和半乳糖凝集素-1。鉴定出由METH诱导产生的独特蛋白质,可能有助于开发针对使用METH人群的诊断、预防和治疗靶点的新型标志物。