关键词: Differential expression Immunopathogenesis Maedi-Visna virus Ovine progressive pneumonia Pathogenesis RNA-seq Sheep

Mesh : Animals Visna-maedi virus / genetics Lung / virology immunology pathology Sheep Gene Expression Profiling Transcriptome Pneumonia, Progressive Interstitial, of Sheep / genetics virology immunology Protein Interaction Maps Gene Expression Regulation Gene Ontology

来  源:   DOI:10.1186/s12864-024-10448-2   PDF(Pubmed)

Abstract:
BACKGROUND: Maedi-visna virus (MVV) is a lentivirus that infects monocyte/macrophage lineage cells in sheep, goats, and wild ruminants and causes pneumonia, mastitis, arthritis, and encephalitis. The immune response to MVV infection is complex, and a complete understanding of its infection and pathogenesis is lacking. This study investigated the in vivo transcriptomic patterns of lung tissues in sheep exposed to MVV using the RNA sequencing technology.
RESULTS: The results indicated that 2,739 genes were significantly differentially expressed, with 1,643 downregulated genes and 1,096 upregulated genes. Many variables that could be unique to MVV infections were discovered. Gene Ontology analysis revealed that a significant proportion of genes was enriched in terms directly related to the immune system and biological responses to viral infections. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the most enriched pathways were related to virus-host cell interactions and inflammatory responses. Numerous immune-related genes, including those encoding several cytokines and interferon regulatory factors, were identified in the protein-protein interaction network of differentially expressed genes (DEGs). The expression of DEGs was evaluated using real-time polymerase chain reaction and western blot analysis. CXCL13, CXCL6, CXCL11, CCR1, CXCL8, CXCL9, CXCL10, TNFSF8, TNFRSF8, IL7R, IFN-γ, CCL2, and MMP9 were upregulated. Immunohistochemical analysis was performed to identify the types of immune cells that infiltrated MVV-infected tissues. B cells, CD4+ and CD8+ T cells, and macrophages were the most prevalent immune cells correlated with MVV infection in the lungs.
CONCLUSIONS: Overall, the findings of this study provide a comprehensive understanding of the in vivo host response to MVV infection and offer new perspectives on the gene regulatory networks that underlie pathogenesis in natural hosts.
摘要:
背景:Maedi-visna病毒(MVV)是一种感染绵羊单核细胞/巨噬细胞谱系细胞的慢病毒,山羊,和野生反刍动物,导致肺炎,乳腺炎,关节炎,和脑炎。对MVV感染的免疫反应是复杂的,缺乏对其感染和发病机制的全面了解。本研究使用RNA测序技术研究了暴露于MVV的绵羊的肺组织的体内转录组模式。
结果:结果表明2,739个基因显著差异表达,1,643个下调基因和1,096个上调基因。发现了许多对于MVV感染可能是独特的变量。基因本体论分析显示,在与免疫系统和对病毒感染的生物学反应直接相关的方面,有很大比例的基因被富集。《京都基因和基因组百科全书》分析显示,最丰富的途径与病毒-宿主细胞相互作用和炎症反应有关。许多免疫相关基因,包括编码几种细胞因子和干扰素调节因子的那些,在差异表达基因(DEGs)的蛋白质-蛋白质相互作用网络中进行了鉴定。使用实时聚合酶链反应和蛋白质印迹分析评估DEGs的表达。CXCL13、CXCL6、CXCL11、CCR1、CXCL8、CXCL9、CXCL10、TNFSF8、TNFRSF8、IL7R、IFN-γ,CCL2和MMP9上调。进行免疫组织化学分析以鉴定浸润MVV感染组织的免疫细胞的类型。B细胞,CD4+和CD8+T细胞,巨噬细胞是与肺部MVV感染相关的最普遍的免疫细胞。
结论:总体而言,这项研究的发现提供了对体内宿主对MVV感染反应的全面理解,并为自然宿主发病机制的基因调控网络提供了新的视角.
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