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艾滋病合并HIV相关脑炎和痴呆患者的基因表达谱及蛋白质-蛋白质相互作用网络分析

Gene expression profiles and protein-protein interaction network analysis in AIDS patients with HIV-associated encephalitis and dementia.

作者信息

Shityakov Sergey, Dandekar Thomas, Förster Carola

机构信息

Department of Anesthesia and Critical Care, University of Würzburg, Würzburg, Germany.

Department of Bioinformatics, University of Würzburg, Würzburg, Germany.

出版信息

HIV AIDS (Auckl). 2015 Nov 18;7:265-76. doi: 10.2147/HIV.S88438. eCollection 2015.

Abstract

Central nervous system dysfunction is an important cause of morbidity and mortality in patients with human immunodeficiency virus type 1 (HIV-1) infection and acquired immunodeficiency virus syndrome (AIDS). Patients with AIDS are usually affected by HIV-associated encephalitis (HIVE) with viral replication limited to cells of monocyte origin. To examine the molecular mechanisms underlying HIVE-induced dementia, the GSE4755 Affymetrix data were obtained from the Gene Expression Omnibus database and the differentially expressed genes (DEGs) between the samples from AIDS patients with and without apparent features of HIVE-induced dementia were identified. In addition, protein-protein interaction networks were constructed by mapping DEGs into protein-protein interaction data to identify the pathways that these DEGs are involved in. The results revealed that the expression of 1,528 DEGs is mainly involved in the immune response, regulation of cell proliferation, cellular response to inflammation, signal transduction, and viral replication cycle. Heat-shock protein alpha, class A member 1 (HSP90AA1), and fibronectin 1 were detected as hub nodes with degree values >130. In conclusion, the results indicate that HSP90A and fibronectin 1 play important roles in HIVE pathogenesis.

摘要

中枢神经系统功能障碍是1型人类免疫缺陷病毒(HIV-1)感染和获得性免疫缺陷综合征(AIDS)患者发病和死亡的重要原因。艾滋病患者通常会受到与HIV相关的脑炎(HIVE)影响,病毒复制仅限于单核细胞来源的细胞。为了研究HIVE诱导痴呆的分子机制,从基因表达综合数据库中获取了GSE4755 Affymetrix数据,并鉴定了有和没有HIVE诱导痴呆明显特征的艾滋病患者样本之间的差异表达基因(DEG)。此外,通过将DEG映射到蛋白质-蛋白质相互作用数据中来构建蛋白质-蛋白质相互作用网络,以识别这些DEG所涉及的途径。结果显示,1528个DEG的表达主要参与免疫反应、细胞增殖调节、细胞对炎症的反应、信号转导和病毒复制周期。热休克蛋白α,A类成员1(HSP90AA1)和纤连蛋白1被检测为度值>130的枢纽节点。总之,结果表明HSP90A和纤连蛋白1在HIVE发病机制中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0610/4655943/15a073569fef/hiv-7-265Fig1.jpg

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