Analysis of Host Gene Expression Profile in HIV-1 and HIV-2 Infected T-Cells

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的复制受到宿主因子（host factors）构成的复杂通路的严密调控，其中诸多因子是细胞嗜性与宿主对HIV感染易感性的决定因素。已知这些宿主因子对HIV两大亚型——HIV-1与HIV-2的复制发挥正向或负向调控作用，进而调节病毒感染性、宿主抗感染应答，最终影响两类病毒特有的疾病进展特征。阐明宿主细胞因子在HIV-1与HIV-2感染后的差异调控机制，有助于理解二者在疾病进展速率与致病机制上的显著差异。该研究成果将助力新型生物标志物的发现，这些标志物可作为诊疗的全新靶点。本研究旨在解析宿主基因在HIV-1/HIV-2感染后的差异表达特征。为达成该目标，我们借助安捷伦全人类基因组寡核苷酸微阵列（Agilent Whole Human Genome Oligo Microarray），在RNA水平上分析了HIV-1(MN株)与HIV-2(ROD株)感染对外周血单个核细胞（peripheral blood mononuclear cells，PBMC）内宿主因子表达的影响。研究团队鉴定了差异表达基因，并明确了其生物学功能。宿主基因表达谱发生显著改变。基因表达谱分析鉴定出HIV-1与HIV-2感染细胞中存在一组差异表达基因。HIV-1感染细胞中，涉及细胞代谢、细胞凋亡、免疫细胞增殖与活化、细胞因子、趋化因子以及转录因子的基因呈现差异表达。而HIV-2感染细胞中差异表达的基因数量相对较少。