Gene expression profiles of HIV-1-infected glia and brain: toward better understanding of the role of astrocytes in HIV-1-associated neurocognitive disorders.
Gene expression profiles of HIV-1-infected glia and brain: toward better understanding of the role of astrocytes in HIV-1-associated neurocognitive disorders.
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DOI：
10.1007/s11481-009-9167-1
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发表时间：
2010-03
影响因子：
6.2
通讯作者：
Volsky, David J.
中科院分区：
文献类型：
--
作者：
Borjabad, Alejandra;Brooks, Andrew I.;Volsky, David J.
关键词：
星形胶质细胞是中枢神经系统 (CNS) 的主要细胞组成部分，它们在大脑发育、正常大脑功能以及中枢神经系统对病原体和损伤的反应中发挥多种作用。星形胶质细胞的功能多样性与它们通过细胞基因表达的精心策划的变化来响应各种生物刺激的能力有关。基因表达程序的失调（通常是由于长期暴露于致病刺激）可能导致星形胶质细胞功能障碍并导致神经发病。在这里，我们回顾了利用功能基因组学来表征 HIV-1 和病毒致病蛋白对星形胶质细胞体外细胞基因表达的影响的研究。我们还首次对培养物中暴露于 HIV-1 的原代小鼠星形胶质细胞进行了微阵列分析。尽管使用了不同的实验条件和微阵列平台，但星形胶质细胞阵列数据集的比较揭示了几种常见的基因调控变化，这些变化可能是这些细胞对 HIV-1 及其蛋白质的反应的基础。我们还将星形胶质细胞的转录谱与 HIV-1 痴呆患者和感染猿免疫缺陷病毒 (SIV) 的猕猴脑组织分析中获得的转录谱进行了比较。值得注意的是，培养的星形胶质细胞中对 HIV-1 反应的许多基因特征在 HIV-1 或 SIV 感染的大脑中也发生了改变。功能基因组学与其他方法相结合，可能有助于阐明星形胶质细胞在 HIV-1 神经发病机制中的作用。
Astrocytes are the major cellular component of the central nervous system (CNS), and they play multiple roles in brain development, normal brain function, and CNS responses to pathogens and injury. The functional versatility of astrocytes is linked to their ability to respond to a wide array of biological stimuli through finely orchestrated changes in cellular gene expression. Dysregulation of gene expression programs, generally by chronic exposure to pathogenic stimuli, may lead to dysfunction of astrocytes and contribute to neuropathogenesis. Here, we review studies that employ functional genomics to characterize the effects of HIV-1 and viral pathogenic proteins on cellular gene expression in astrocytes in vitro. We also present the first microarray analysis of primary mouse astrocytes exposed to HIV-1 in culture. In spite of different experimental conditions and microarray platforms used, comparison of the astrocyte array data sets reveals several common gene-regulatory changes that may underlie responses of these cells to HIV-1 and its proteins. We also compared the transcriptional profiles of astrocytes with those obtained in analyses of brain tissues of patients with HIV-1 dementia and macaques infected with simian immunodeficiency virus (SIV). Notably, many of the gene characteristics of responses to HIV-1 in cultured astrocytes were also altered in HIV-1 or SIV-infected brains. Functional genomics, in conjunction with other approaches, may help clarify the role of astrocytes in HIV-1 neuropathogenesis.
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