Medicine College of Yan'an University, Yan'an, Shaanxi, P. R. China.
Department of Urology, Yangling Demonstration Zone Hospital, Yangling, Shaanxi, P. R. China.
J Med Virol. 2018 Jul;90(7):1199-1209. doi: 10.1002/jmv.25071. Epub 2018 Mar 30.
Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4 and CD8 T cells. The numbers of CD4 and CD8 T cells of HIV infected individuals were analyzed and the GEO database (GSE6740) was screened for differentially expressed genes (DEGs) in HIV infected CD4 and CD8 T cells. Gene Ontology enrichment, KEGG pathway analyses, and protein-protein interaction (PPI) network were performed to identify the key pathway and core proteins in anti-HIV virus process of CD4 and CD8 T cells. Finally, we analyzed the expressions of key proteins in HIV-infected T cells (GSE6740 dataset) and peripheral blood mononuclear cells(PBMCs) (GSE511 dataset). 1) CD4 T cells counts and ratio of CD4 /CD8 T cells decreased while CD8 T cells counts increased in HIV positive individuals; 2) 517 DEGs were found in HIV infected CD4 and CD8 T cells at acute and chronic stage with the criterial of P-value <0.05 and fold change (FC) ≥2; 3) In acute HIV infection, type 1 interferon (IFN-1) pathway might played a critical role in response to HIV infection of T cells. The main biological processes of the DEGs were response to virus and defense response to virus. At chronic stage, ISG15 protein, in conjunction with IFN-1 pathway might play key roles in anti-HIV responses of CD4 T cells; and 4) The expression of ISG15 increased in both T cells and PBMCs after HIV infection. Gene expression profile of CD4 and CD8 T cells changed significantly in HIV infection, in which ISG15 gene may play a central role in activating the natural antiviral process of immune cells.
进行了全面的生物信息学分析，以探讨 CD4 和 CD8 T 细胞对 HIV 感染反应的关键生物标志物。分析了 HIV 感染者的 CD4 和 CD8 T 细胞数量，并筛选了 GEO 数据库（GSE6740）中 HIV 感染的 CD4 和 CD8 T 细胞中的差异表达基因（DEGs）。进行了基因本体论富集、KEGG 通路分析和蛋白质-蛋白质相互作用（PPI）网络分析，以确定 CD4 和 CD8 T 细胞抗 HIV 病毒过程中的关键途径和核心蛋白。最后，我们分析了 HIV 感染的 T 细胞（GSE6740 数据集）和外周血单核细胞（PBMCs）（GSE511 数据集）中关键蛋白的表达。1）HIV 阳性个体的 CD4 T 细胞计数和 CD4/CD8 T 细胞比值降低，而 CD8 T 细胞计数增加；2）在急性和慢性 HIV 感染的 CD4 和 CD8 T 细胞中发现了 517 个 DEGs，其标准为 P 值<0.05 和倍数变化（FC）≥2；3）在急性 HIV 感染中，I 型干扰素（IFN-1）途径可能在 T 细胞对 HIV 感染的反应中发挥关键作用。DEGs 的主要生物学过程是对病毒的反应和对病毒的防御反应。在慢性阶段，ISG15 蛋白与 IFN-1 途径可能在 CD4 T 细胞的抗 HIV 反应中发挥关键作用；4）HIV 感染后 T 细胞和 PBMCs 中的 ISG15 表达增加。HIV 感染后 CD4 和 CD8 T 细胞的基因表达谱发生了显著变化，其中 ISG15 基因可能在激活免疫细胞的天然抗病毒过程中发挥核心作用。
