Transcriptomic Analysis of Respiratory Tissue and Cell Line Models to Examine Glycosylation Machinery during SARS-CoV-2 Infection.
Transcriptomic Analysis of Respiratory Tissue and Cell Line Models to Examine Glycosylation Machinery during SARS-CoV-2 Infection.
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DOI：
10.3390/v13010082
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发表时间：
2021-01-08
期刊：
影响因子：
--
通讯作者：
Joshi L
中科院分区：
文献类型：
--
作者：
Oommen A;Cunningham S;Joshi L
糖基化是最丰富的翻译后修饰，在感染免疫应答中对蛋白质和大分子的表达、定位和功能有着深远的影响。本文介绍了利用公共存储库的高通量功能基因组学数据进行转录组学分析的结果，以检查人类糖基化机制在响应SARS-CoV-2刺激和感染时的转录改变。除了常规的计算机功能富集分析方法外，我们还介绍了生物医学文献数据库的人工分析结果，以揭示聚糖和聚糖结合蛋白在SARS-CoV-2感染期间调节宿主免疫反应的生物学意义。我们的分析揭示了关键的免疫调节凝集素、蛋白聚糖和聚糖表位，除了作为SARS-CoV-2病原体的粘附受体的重要作用外，还涉及发挥阴性和阳性下游炎症信号通路。提出了一种假设的人类糖基因差异表达与宿主炎症反应的改变和对SARS-CoV-2病原体产生的细胞因子风暴之间的相关性。这些标志物可以为SARS-CoV-2调节的糖基化途径的不同作用和功能提供新的见解，为COVID-19免疫和其他病毒感染因子提供分层、治疗和靶向方法的途径。
Glycosylation, being the most abundant post-translational modification, plays a profound role affecting expression, localization and function of proteins and macromolecules in immune response to infection. Presented are the findings of a transcriptomic analysis performed using high-throughput functional genomics data from public repository to examine the altered transcription of the human glycosylation machinery in response to SARS-CoV-2 stimulus and infection. In addition to the conventional in silico functional enrichment analysis methods we also present results from the manual analysis of biomedical literature databases to bring about the biological significance of glycans and glycan-binding proteins in modulating the host immune response during SARS-CoV-2 infection. Our analysis revealed key immunomodulatory lectins, proteoglycans and glycan epitopes implicated in exerting both negative and positive downstream inflammatory signaling pathways, in addition to its vital role as adhesion receptors for SARS-CoV-2 pathogen. A hypothetical correlation of the differentially expressed human glycogenes with the altered host inflammatory response and the cytokine storm-generated in response to SARS-CoV-2 pathogen is proposed. These markers can provide novel insights into the diverse roles and functioning of glycosylation pathways modulated by SARS-CoV-2, provide avenues of stratification, treatment, and targeted approaches for COVID-19 immunity and other viral infectious agents.
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