• 中文核心期刊
  • CSCD来源期刊
  • 中国科技核心期刊
  • CA、CABI、ZR收录期刊

伪狂犬病病毒感染小鼠脾脏的病理特征及转录组分析

Pathological Observations and Transcriptome Sequencing on Spleens of Pseudorabies Virus-infected Mice

  • 摘要:
    目的 探究伪狂犬病病毒(pseudorabies virus, PRV)诱导小鼠脾脏的病理损伤及其调控机制,为后续解析PRV的免疫逃逸机制、筛选抗病毒靶点奠定理论基础。
    方法 使用PRV变异株SX-2018感染BALB/c小鼠,分别收集感染组与对照组小鼠的脾脏,首先进行组织病理学观察,然后将收集的脾脏组织进行转录组测序分析。
    结果 SX-2018感染可导致小鼠脾脏明显的病理损伤,主要表现为:脾髓内淋巴细胞坏死、丢失,巨噬细胞增多。转录组测序分析共筛选出 656 个差异表达基因,其中上调基因299 个、下调基因357 个。通过GO 富集分析和KEGG富集分析发现,显著差异基因主要富集于细胞因子-细胞因子受体相互作用和MAPK 信号通路;选取差异显著的7条基因进行荧光定量PCR 验证,验证结果与测序数据一致。
    结论 PRV变异株感染可导致小鼠脾脏结构损伤、免疫细胞亚群失衡,其损伤过程与细胞因子-细胞因子受体相互作用、MAPK 信号通路的基因调控密切相关。

     

    Abstract:
    Objective Damage on the spleens of mice inoculated with pseudorabies virus (PRV) and pathological regulatory mechanism of the infection were studied, to lay a theoretical foundation for the immune escape mechanism and antiviral targets screening of PRV.
    Method BALB/c mice were inoculated with the PRV variant strain SX-2018, along with healthy ones as control, prior to histopathological observations and transcriptomic sequencing on spleens of the animals.
    Result SX-2018-infected mice showed significant injury on the spleens with the characteristic lymphocyte necrosis in the parenchyma and increased macrophages. The transcriptomic sequencing on the tissue cells identified 299 upregulated and 357 downregulated differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses indicated that these DEGs were predominantly enriched in the cytokine-cytokine receptor interaction and mitogen-activated protein kinase (MAPK) signaling pathways. Seven representative DEGs were subsequently validated by fluorescence quantitative PCR (qPCR) to yield a highly consistent result with RNA-seq.
    Conclusion The PRV-infected mice exhibited significant structural pathology on spleen with disrupted homeostasis of immune cell subsets. The infection was closely associated with the dysregulated gene expressions in cytokine–cytokine receptor interaction and MAPK signaling pathways of the animal.

     

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