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2000 - 2006年HIV - 1对免疫细胞基因调控的微阵列数据。

Microarray data on gene modulation by HIV-1 in immune cells: 2000-2006.

作者信息

Giri Malavika S, Nebozhyn Michael, Showe Louise, Montaner Luis J

机构信息

HIV Immunopathogenesis Laboratory, Wistar Institute, 3601 Spruce St., Room 480, Philadelphia, PA 19104, USA.

出版信息

J Leukoc Biol. 2006 Nov;80(5):1031-43. doi: 10.1189/jlb.0306157. Epub 2006 Aug 29.

Abstract

Here, we review 34 HIV microarray studies in human immune cells over the period of 2000-March 2006 with emphasis on analytical approaches used and conceptual advances on HIV modulation of target cells (CD4 T cell, macrophage) and nontargets such as NK cell, B cell, and dendritic cell subsets. Results to date address advances on gene modulation associated with immune dysregulation, susceptibility to apoptosis, virus replication, and viral persistence following in vitro or in vivo infection/exposure to HIV-1 virus or HIV-1 accessory proteins. In addition to gene modulation associated with known functional correlates of HIV infection and replication (e.g., T cell apoptosis), microarray data have yielded novel, potential mechanisms of HIV-mediated pathogenesis such as modulation of cholesterol biosynthetic genes in CD4 T cells (relevant to virus replication and infectivity) and modulation of proteasomes and histone deacetylases in chronically infected cell lines (relevant to virus latency). Intrinsic challenges in summarizing gene modulation studies remain in development of sound approaches for comparing data obtained using different platforms and analytical tools, deriving unifying concepts to distil the large volumes of data collected, and the necessity to impose a focus for validation on a small fraction of genes. Notwithstanding these challenges, the field overall continues to demonstrate progress in expanding the pool of target genes validated to date in in vitro and in vivo datasets and understanding the functional correlates of gene modulation to HIV-1 pathogenesis in vivo.

摘要

在此,我们回顾了2000年至2006年3月期间针对人类免疫细胞开展的34项HIV微阵列研究,重点关注所使用的分析方法以及HIV对靶细胞(CD4 T细胞、巨噬细胞)和非靶细胞(如NK细胞、B细胞和树突状细胞亚群)调节方面的概念进展。迄今为止的研究结果涉及与免疫失调、细胞凋亡易感性、病毒复制以及体外或体内感染/暴露于HIV-1病毒或HIV-1辅助蛋白后病毒持续性相关的基因调节进展。除了与HIV感染和复制的已知功能关联(如T细胞凋亡)相关的基因调节外,微阵列数据还揭示了HIV介导发病机制的新的潜在机制,如CD4 T细胞中胆固醇生物合成基因的调节(与病毒复制和感染性相关)以及慢性感染细胞系中蛋白酶体和组蛋白脱乙酰酶的调节(与病毒潜伏相关)。总结基因调节研究面临的固有挑战仍然存在于开发合理的方法以比较使用不同平台和分析工具获得的数据、推导统一概念以提炼所收集的大量数据,以及有必要聚焦于对一小部分基因进行验证。尽管存在这些挑战,但总体而言,该领域在扩大迄今在体外和体内数据集中已验证的靶基因库以及理解基因调节与HIV-1体内发病机制的功能关联方面继续取得进展。

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