Devadas Krishnakumar, Biswas Santanu, Haleyurgirisetty Mohan, Wood Owen, Ragupathy Viswanath, Lee Sherwin, Hewlett Indira
Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-0002, United States of America.
PLoS One. 2016 Jan 28;11(1):e0147421. doi: 10.1371/journal.pone.0147421. eCollection 2016.
HIV replication is closely regulated by a complex pathway of host factors, many of them being determinants of cell tropism and host susceptibility to HIV infection. These host factors are known to exert a positive or negative influence on the replication of the two major types of HIV, HIV-1 and HIV-2, thereby modulating virus infectivity, host response to infection and ultimately disease progression profiles characteristic of these two types. Understanding the differential regulation of host cellular factors in response to HIV-1 and HIV-2 infections will help us to understand the apparent differences in rates of disease progression and pathogenesis. This knowledge would aid in the discovery of new biomarkers that may serve as novel targets for therapy and diagnosis. The objective of this study was to determine the differential expression of host genes in response to HIV-1/HIV-2 infection. To achieve this, we analyzed the effects of HIV-1 (MN) and HIV-2 (ROD) infection on the expression of host factors in PBMC at the RNA level using the Agilent Whole Human Genome Oligo Microarray. Differentially expressed genes were identified and their biological functions determined. Host gene expression profiles were significantly changed. Gene expression profiling analysis identified a subset of differentially expressed genes in HIV-1 and HIV-2 infected cells. Genes involved in cellular metabolism, apoptosis, immune cell proliferation and activation, cytokines, chemokines, and transcription factors were differentially expressed in HIV-1 infected cells. Relatively few genes were differentially expressed in cells infected with HIV-2.
HIV复制受到宿主因子复杂途径的密切调控,其中许多因子是细胞嗜性和宿主对HIV感染易感性的决定因素。已知这些宿主因子对两种主要类型的HIV,即HIV-1和HIV-2的复制产生正向或负向影响,从而调节病毒感染性、宿主对感染的反应以及这两种类型所特有的疾病进展特征。了解宿主细胞因子对HIV-1和HIV-2感染的差异调节将有助于我们理解疾病进展速度和发病机制的明显差异。这些知识将有助于发现新的生物标志物,这些标志物可作为治疗和诊断的新靶点。本研究的目的是确定宿主基因对HIV-1/HIV-2感染的差异表达。为实现这一目标,我们使用安捷伦全人类基因组寡核苷酸微阵列在RNA水平分析了HIV-1(MN)和HIV-2(ROD)感染对PBMC中宿主因子表达的影响。鉴定了差异表达基因并确定了它们的生物学功能。宿主基因表达谱发生了显著变化。基因表达谱分析在HIV-1和HIV-2感染的细胞中鉴定出一组差异表达基因。参与细胞代谢、凋亡、免疫细胞增殖和激活、细胞因子、趋化因子和转录因子的基因在HIV-1感染的细胞中差异表达。在感染HIV-2的细胞中差异表达的基因相对较少。