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转录组分析呼吸道组织和细胞系模型,以研究 SARS-CoV-2 感染期间的糖基化机制。

Transcriptomic Analysis of Respiratory Tissue and Cell Line Models to Examine Glycosylation Machinery during SARS-CoV-2 Infection.

机构信息

Advanced Glycoscience Research Cluster (AGRC), National University of Ireland Galway, H91 TK33 Galway, Ireland.

Centre for Research in Medical Devices (CURAM), National University of Ireland Galway, H91 TK33 Galway, Ireland.

出版信息

Viruses. 2021 Jan 8;13(1):82. doi: 10.3390/v13010082.

Abstract

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.

摘要

糖基化是最丰富的翻译后修饰之一,对蛋白质和大分子在感染免疫反应中的表达、定位和功能有深远的影响。本文介绍了一项转录组分析的结果,该分析使用公共数据库中的高通量功能基因组学数据,研究了人类糖基化机制在 SARS-CoV-2 刺激和感染时的转录变化。除了传统的计算功能富集分析方法外,我们还展示了从生物医学文献数据库进行手动分析的结果,以阐明聚糖和糖结合蛋白在调节 SARS-CoV-2 感染期间宿主免疫反应中的生物学意义。我们的分析揭示了关键的免疫调节凝集素、蛋白聚糖和糖基化表位,它们在发挥负向和正向下游炎症信号通路方面发挥作用,此外,它们还是 SARS-CoV-2 病原体的黏附受体。提出了差异表达的人类糖基因与宿主炎症反应的改变以及 SARS-CoV-2 病原体产生的细胞因子风暴之间的假设相关性。这些标志物可以为 SARS-CoV-2 调节的糖基化途径的多种作用和功能提供新的见解,并为 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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/270e/7827443/446b258d2063/viruses-13-00082-g001a.jpg

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