汉坦病毒感染后血管内皮细胞及外周血单细胞基因表达差异生物信息学分析及防治药物筛选

    Bioinformatics analysis of gene expressions in vascular endothelial cells and peripheral blood single cells after Hantavirus infection and drug screening

      摘要
    • 摘要:
      目的 探讨汉坦病毒（Hantan virus，HTV）感染对血管内皮细胞及外周血细胞基因表达的影响和潜在的病理机制以及可能的治疗靶点。
      方法 通过基因表达综合数据库（gene expression omnibus，GEO）分别获取HTV数据集转录组GSE133751（3例HTV、3例对照）和单细胞测序数据集GSE161354（6例HTV、2例对照）进行联合分析。通过筛选确定了HTV对于血管内皮细胞的影响以及其中的差异表达基因（differentially expressed genes，DEGs），并进行功能富集分析。结合HTV患者血液单细胞测序数据分析疾病相关的细胞亚型、关键基因以及细胞之间的互作关系。基于分子对接结果筛选潜在的疾病治疗药物。
      结果 通过对GSE133751的数据集分析，共获取了338个差异基因，包含288个上调基因以及50个下调基因，通过GO以及KEGG功能富集揭示了主要的相关功能与抗病毒以及炎性功能相关。结合单细胞数据GSE161354联合分析定位了与疾病相关的细胞类型：CD4_Naive_T_cell，并定位了其中的核心基因TXNIP以及IL7R。通过分子对接对TXNIP以及IL7R进行药物预测，最终获得了雷迪帕韦（Ledipasvir）与利福昔明（Rifaximin）两个可能的靶向药物。
      结论 本研究筛选和定位了HTV感染后内皮细胞及外周血细胞中基因表达差异，并确定核心基因以及关键细胞亚型。进而，通过分子对接筛选获得了潜在的HTV感染后循环系统损伤的治疗药物，为HTV感染患者的临床治疗提供新的实验依据。

       

      Abstract:
      AIM  To explore the effects of Hantavirus (HTV) infection on gene expressions, potential pathological mechanism and possible therapeutic targets in vascular endothelial cells and peripheral blood cells.
      METHODS  We analyzed two HTV datasets, GSE133751 (3 HTV cases, 3 controls) and GSE161354 (7 HTV cases, 3 controls), obtained from the Gene Expression Omnibus (GEO), identified differentially expressed genes (DEGs) and performed functional enrichment to explore related functions. Additionally, we analyzed disease-related cell subtypes, key genes and cell-cell interactions using single-cell sequencing data from HTV patients’ blood. Potential therapeutic drugs were screened based on molecular docking results.
      RESULTS  Analysis of the GSE133751 dataset yielded 338 DEGs, with 288 up-regulated and 50 down-regulated genes. Functional enrichment indicated that these genes were primarily associated with antiviral and inflammatory responses. Using the single-cell dataset GSE161354, we identified CD4_Naive_T_cell as a disease-associated cell type and TXNIP and IL7R as core genes. Molecular docking suggested Ledipasvir and Rifaximin as potential therapeutic agents.
      CONCLUSION  This study reveals differential gene expressions in HTV-infected vascular endothelial cells and peripheral blood cells, identifies core genes and key cellular subtypes and suggests potential target drugs through molecular docking. These findings provide a new experimental foundation for the clinical management of HTV infection.

       

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