Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Curr HIV/AIDS Rep. 2012 Mar;9(1):34-43. doi: 10.1007/s11904-011-0100-x.
HIV-1-infected individuals exhibit remarkable variation in the onset of disease. Virus replication and disease progression depend on host cellular transcription and gene regulation in virus-specific target cells. Both viral and host factors are implicated in this differential regulation. Gene arrays and transcriptome analyses might shed light on why some infected individuals remain asymptomatic while others progress rapidly to AIDS. Here we review developments in HIV research using gene array technologies and the unifying concepts that have emerged from these studies. Gene set enrichment analysis has revealed gene signatures linked to disease progression involving pathways related to metabolism, apoptosis, cell-cycle dysregulation, and T-cell signaling. Macrophages contain anti-apoptotic signatures. Also, HIV-1 regulates previously under-emphasized cholesterol biosynthesis and energy production pathways. Notably, cellular pathways linked to a subset of HIV-infected individuals known as non-progressors contribute to survival and anti-viral responses.
HIV-1 感染者在疾病发作方面表现出显著的差异。病毒复制和疾病进展取决于病毒特异性靶细胞中宿主细胞的转录和基因调控。病毒和宿主因素都与这种差异调节有关。基因阵列和转录组分析可能有助于阐明为什么一些感染者仍然无症状,而另一些人则迅速进展为艾滋病。在这里,我们回顾了使用基因阵列技术进行 HIV 研究的进展情况,以及这些研究中出现的统一概念。基因集富集分析揭示了与涉及代谢、细胞凋亡、细胞周期失调和 T 细胞信号转导等途径相关的疾病进展相关的基因特征。巨噬细胞含有抗凋亡特征。此外,HIV-1 还调节先前被低估的胆固醇生物合成和能量产生途径。值得注意的是,与被称为非进展者的一部分 HIV 感染者相关的细胞途径有助于存活和抗病毒反应。