Metabolic changes during respiratory syncytial virus infection of epithelial cells

Metabolic changes during respiratory syncytial virus infection of epithelial cells
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DOI:
10.1371/journal.pone.0230844
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发表时间:
2020-03-26
期刊:
影响因子:
3.7
通讯作者:
Martinez, Isidoro
Martinez, Isidoro
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Martin-Vicente, Maria;Gonzalez-Riano, Carolina;Martinez, Isidoro

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病毒感染会引起受感染细胞的显着代谢变化,以优化病毒的产生,同时细胞会制定对策来限制感染。人呼吸道合胞病毒 (HRSV) 是一种传染性病原体,可导致婴儿、老年人和免疫功能低下的成人严重下呼吸道感染 (LRTI),目前尚无有效的治疗方法或疫苗。在本研究中,利用甲醇细胞提取物的液相色谱/质谱分析,通过非靶向代谢组学研究了上皮细胞HRSV感染后不同时间点代谢物水平的变化。感染后18小时后,许多代谢物显着上调,包括核苷酸、氨基酸、氨基和核苷酸糖以及中心碳途径的代谢物。相比之下,大多数脂质类别均下调。此外,氧化谷胱甘肽和多胺水平的增加与受感染细胞的氧化应激有关。这些结果显示了 HRSV 感染如何影响细胞代谢以产生病毒繁殖所需的能量和构建模块,这表明针对该病毒的潜在治疗干预措施。
Viral infections induce substantial metabolic changes in infected cells to optimize viral production while cells develop countermeasures to restrict that infection. Human respiratory syncytial virus (HRSV) is an infectious pathogen that causes severe lower respiratory tract infections (LRTI) in infants, the elderly, and immunocompromised adults for which no effective treatment or vaccine is currently available. In this study, variations in metabolite levels at different time points post-HRSV infection of epithelial cells were studied by untargeted metabolomics using liquid chromatography/mass spectrometry analysis of methanol cell extracts. Numerous metabolites were significantly upregulated after 18 hours post-infection, including nucleotides, amino acids, amino and nucleotide sugars, and metabolites of the central carbon pathway. In contrast, most lipid classes were downregulated. Additionally, increased levels of oxidized glutathione and polyamines were associated with oxidative stress in infected cells. These results show how HRSV infection influences cell metabolism to produce the energy and building blocks necessary for virus reproduction, suggesting potential therapeutic interventions against this virus.