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Influenza A virus infects pulmonary microvascular endothelial cells leading to microvascular leakage and release of pro-inflammatory cytokines
PeerJ ( IF 2.3 ) Pub Date : 2021-08-03 , DOI: 10.7717/peerj.11892
Tiantian Han 1 , Yanni Lai 1 , Yong Jiang 2 , Xiaohong Liu 3 , Danhua Li 4
Affiliation  

Objective To investigate the replication of influenza A virus A/Puerto Rico/8/34 (H1N1) in pulmonary microvascular endothelial cells and its effect on endothelial barrier function. Methods Human pulmonary microvascular endothelial cells were infected with influenza A/Puerto Rico/8/34 (H1N1) virus. Plaque reduction assay, real-time quantitative PCR, immunofluorescence staining, and western blot were used to elucidate the replication process of virus-infected endothelial cells. In addition, real-time quantitative PCR was used to detect the relative expression levels of mRNA of some inflammatory factors. The endothelial resistance assay was used to determine the permeability of the endothelial monolayer. Excavation and analysis of data from open databases, such as the GeneCards database, DAVID Bioinformatics Resources, STRING search tool, and DGIdb database determined the genes, proteins, and signal pathways related to microvascular leakage caused by the H1N1 virus, and predicted the drugs that could be effective for treatment. Results In vitro experiments showed that the influenza virus can infect endothelial cells, leading to a significant increase in the permeability of pulmonary microvascular endothelial cells and the release of pro-inflammatory cytokines, but does not efficiently replicate in endothelial cells. A total of 107 disease-related target genes were obtained from the Gene-cards database. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these genes mainly affected the pathways related to “Inflammatory bowel disease” (IBD), “Chagas disease” (American trypanosomiasis), “Influenza A”, and also played a key role in anti-inflammation and regulation of immunity. After enrichment analysis, 46 hub genes were screened. A total of 42 FDA-approved drugs corresponding to the hub genes were screened from the DGIdb database, and these could be formulated for topical application. In addition, these drugs can be used to treat other diseases, including cancer, inflammatory diseases, immune system disorders, and cardiovascular diseases. Conclusion H1N1 influenza virus affects the barrier function of endothelial cells indirectly. Combined with bioinformatics tools, we can better understand the possible mechanism of action of influenza A (H1N1) virus causing pulmonary microvascular leakage and provide new clues for the treatment of pulmonary microvascular leakage.

中文翻译:

甲型流感病毒感染肺微血管内皮细胞,导致微血管渗漏和促炎细胞因子释放

目的探讨甲型流感病毒A/Puerto Rico/8/34(H1N1)在肺微血管内皮细胞中的复制及其对内皮屏障功能的影响。方法用甲型/波多黎各/8/34(H1N1)流感病毒感染人肺微血管内皮细胞。使用斑块减少测定、实时定量 PCR、免疫荧光染色和蛋白质印迹来阐明病毒感染的内皮细胞的复制过程。此外,采用实时定量PCR检测部分炎症因子mRNA的相对表达水平。内皮电阻测定用于确定内皮单层的通透性。挖掘和分析来自开放数据库的数据,例如 GeneCards 数据库、DAVID 生物信息学资源、STRING 搜索工具、DGIdb数据库确定了与H1N1病毒引起的微血管渗漏相关的基因、蛋白质和信号通路,并预测了可能有效治疗的药物。结果体外实验表明,流感病毒可以感染内皮细胞,导致肺微血管内皮细胞通透性显着增加,促炎细胞因子释放,但在内皮细胞中不能有效复制。从 Gene-cards 数据库中总共获得了 107 个疾病相关的靶基因。京都基因和基因组百科全书(KEGG)富集分析表明,这些基因主要影响与“炎症性肠病”(IBD)、“南美锥虫病”(美洲锥虫病)、“甲型流感”、在抗炎和调节免疫方面也发挥了关键作用。经过富集分析,筛选出46个hub基因。从 DGIdb 数据库中筛选出与中心基因相对应的 42 种 FDA 批准的药物,这些药物可以配制用于局部应用。此外,这些药物还可用于治疗其他疾病,包括癌症、炎症性疾病、免疫系统疾病和心血管疾病。结论 H1N1流感病毒间接影响内皮细胞的屏障功能。结合生物信息学工具,可以更好地了解甲型H1N1流感病毒引起肺微血管渗漏的可能作用机制,为肺微血管渗漏的治疗提供新的线索。从 DGIdb 数据库中筛选出与中心基因相对应的 42 种 FDA 批准的药物,这些药物可以配制用于局部应用。此外,这些药物还可用于治疗其他疾病,包括癌症、炎症性疾病、免疫系统疾病和心血管疾病。结论 H1N1流感病毒间接影响内皮细胞的屏障功能。结合生物信息学工具,可以更好地了解甲型H1N1流感病毒引起肺微血管渗漏的可能作用机制,为肺微血管渗漏的治疗提供新的线索。从 DGIdb 数据库中筛选出与中心基因相对应的 42 种 FDA 批准的药物,这些药物可以配制用于局部应用。此外,这些药物还可用于治疗其他疾病,包括癌症、炎症性疾病、免疫系统疾病和心血管疾病。结论 H1N1流感病毒间接影响内皮细胞的屏障功能。结合生物信息学工具,可以更好地了解甲型H1N1流感病毒引起肺微血管渗漏的可能作用机制,为肺微血管渗漏的治疗提供新的线索。包括癌症、炎症性疾病、免疫系统疾病和心血管疾病。结论 H1N1流感病毒间接影响内皮细胞的屏障功能。结合生物信息学工具,可以更好地了解甲型H1N1流感病毒引起肺微血管渗漏的可能作用机制,为肺微血管渗漏的治疗提供新的线索。包括癌症、炎症性疾病、免疫系统疾病和心血管疾病。结论 H1N1流感病毒间接影响内皮细胞的屏障功能。结合生物信息学工具,可以更好地了解甲型H1N1流感病毒引起肺微血管渗漏的可能作用机制,为肺微血管渗漏的治疗提供新的线索。
更新日期:2021-08-03
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