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Metabolomic Analysis of Influenza A Virus A/WSN/1933 (H1N1) Infected A549 Cells during First Cycle of Viral Replication

机译:甲型流感病毒A / WSN / 1933(H1N1)感染的A549细胞在病毒复制的第一个周期期间的代谢组学分析

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摘要

Influenza A virus (IAV) has developed strategies to utilize host metabolites which, after identification and isolation, can be used to discover the value of immunometabolism. During this study, to mimic the metabolic processes of influenza virus infection in human cells, we infect A549 cells with H1N1 (WSN) influenza virus and explore the metabolites with altered levels during the first cycle of influenza virus infection using ultra-high-pressure liquid chromatography–quadrupole time-of-flight mass spectrometer (UHPLC–Q-TOF MS) technology. We annotate the metabolites using MetaboAnalyst and the Kyoto Encyclopedia of Genes and Genomes pathway analyses, which reveal that IAV regulates the abundance of the metabolic products of host cells during early infection to provide the energy and metabolites required to efficiently complete its own life cycle. These metabolites are correlated with the tricarboxylic acid (TCA) cycle and mainly are involved in purine, lipid, and glutathione metabolisms. Concurrently, the metabolites interact with signal receptors in A549 cells to participate in cellular energy metabolism signaling pathways. Metabonomic analyses have revealed that, in the first cycle, the virus not only hijacks cell metabolism for its own replication, but also affects innate immunity, indicating a need for further study of the complex relationship between IAV and host cells.
机译:甲型流感病毒(IAV)已开发出利用宿主代谢产物的策略,这些宿主代谢产物经过鉴定和分离后可用于发现免疫代谢的价值。在这项研究中,为了模拟人类细胞中流感病毒感染的代谢过程,我们用H1N1(WSN)流感病毒感染A549细胞,并使用超高压液体在流感病毒感染的第一个周期中探索水平发生改变的代谢物色谱-四极杆飞行时间质谱仪(UHPLC-Q-TOF MS)技术。我们使用MetaboAnalyst和《京都议定书》中的基因和基因组途径分析对代谢产物进行注释,这揭示了IAV在早期感染过程中调节宿主细胞代谢产物的丰度,从而提供有效完成其自身生命周期所需的能量和代谢产物。这些代谢物与三羧酸(TCA)循环相关,并且主要参与嘌呤,脂质和谷胱甘肽的代谢。同时,代谢物与A549细胞中的信号受体相互作用,参与细胞能量代谢信号传导途径。代谢组学分析表明,在第一个周期中,该病毒不仅劫持了细胞自身复制的新陈代谢,而且还影响先天免疫力,这表明需要进一步研究IAV与宿主细胞之间的复杂关系。

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