关键词: COVID-19 HIV differentially expressed genes drug chemicals hub genes immune infiltration influenza protein-protein interaction networks

Mesh : Humans Influenza, Human / genetics COVID-19 / genetics SARS-CoV-2 Computational Biology MicroRNAs / genetics Transcription Factors Gene Expression Regulation HIV Infections / drug therapy genetics

来  源:   DOI:10.3389/fimmu.2024.1369311   PDF(Pubmed)

Abstract:
Coronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living with HIV, characterized by compromised immune systems, face an elevated risk of severe outcomes and increased mortality when affected by COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, and HIV remain unclear. Our research endeavors to elucidate the shared pathways and molecular markers in individuals with HIV concurrently infected with COVID-19 and influenza. Furthermore, we aim to identify potential medications that may prove beneficial in managing these three interconnected illnesses.
Sequencing data for COVID-19 (GSE157103), influenza (GSE185576), and HIV (GSE195434) were retrieved from the GEO database. Commonly expressed differentially expressed genes (DEGs) were identified across the three datasets, followed by immune infiltration analysis and diagnostic ROC analysis on the DEGs. Functional enrichment analysis was performed using GO/KEGG and Gene Set Enrichment Analysis (GSEA). Hub genes were screened through a Protein-Protein Interaction networks (PPIs) analysis among DEGs. Analysis of miRNAs, transcription factors, drug chemicals, diseases, and RNA-binding proteins was conducted based on the identified hub genes. Finally, quantitative PCR (qPCR) expression verification was undertaken for selected hub genes.
The analysis of the three datasets revealed a total of 22 shared DEGs, with the majority exhibiting an area under the curve value exceeding 0.7. Functional enrichment analysis with GO/KEGG and GSEA primarily highlighted signaling pathways associated with ribosomes and tumors. The ten identified hub genes included IFI44L, IFI44, RSAD2, ISG15, IFIT3, OAS1, EIF2AK2, IFI27, OASL, and EPSTI1. Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, and hsa-miR-6069), five essential transcription factors (CREB1, CEBPB, EGR1, EP300, and IRF1), and the top ten significant drug chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) were identified.
This research provides valuable insights into shared molecular targets, signaling pathways, drug chemicals, and potential biomarkers for individuals facing the complex intersection of COVID-19, influenza, and HIV. These findings hold promise for enhancing the precision of diagnosis and treatment for individuals with HIV co-infected with COVID-19 and influenza.
摘要:
冠状病毒病(COVID-19),由SARS-CoV-2引起的,已经成为一种传染病,与全球广泛的季节性和零星流感流行共存。艾滋病毒感染者,以免疫系统受损为特征,受COVID-19影响时,面临严重结局风险升高和死亡率增加。尽管有这种联系,连接COVID-19,流感的分子错综复杂,艾滋病毒仍然不清楚。我们的研究努力阐明同时感染COVID-19和流感的HIV个体的共同途径和分子标志物。此外,我们的目标是确定可能被证明对治疗这三种相互关联的疾病有益的潜在药物。
COVID-19(GSE157103)的测序数据,流感(GSE185576),和HIV(GSE195434)从GEO数据库中检索。在三个数据集中鉴定了常见表达的差异表达基因(DEGs),然后对DEGs进行免疫浸润分析和诊断性ROC分析。使用GO/KEGG和基因组富集分析(GSEA)进行功能富集分析。通过DEG之间的蛋白质-蛋白质相互作用网络(PPI)分析筛选了Hub基因。miRNA的分析,转录因子,药物化学品,疾病,和RNA结合蛋白是基于鉴定的hub基因进行的。最后,对选择的hub基因进行定量PCR(qPCR)表达验证。
对三个数据集的分析显示,共有22个共享DEG,大多数曲线下面积值超过0.7。GO/KEGG和GSEA的功能富集分析主要突出了与核糖体和肿瘤相关的信号通路。确定的十个hub基因包括IFI44L,IFI44,RSAD2,ISG15,IFIT3,OAS1,EIF2AK2,IFI27,OASL,和EPSTI1。此外,五个关键的miRNA(hsa-miR-8060,hsa-miR-6890-5p,hsa-miR-5003-3p,hsa-miR-6893-3p,和hsa-miR-6069),五种必需转录因子(CREB1、CEBPB、EGR1、EP300和IRF1),和十大重要药物化学物质(雌二醇,黄体酮,维甲酸,骨化三醇,氟尿嘧啶,甲氨蝶呤,脂多糖,丙戊酸,二氧化硅,环孢菌素)被鉴定。
这项研究为共享分子靶标提供了有价值的见解,信号通路,药物化学品,以及面临COVID-19、流感复杂交集的个体的潜在生物标志物,和艾滋病毒。这些发现有望提高同时感染COVID-19和流感的HIV患者的诊断和治疗的准确性。
公众号