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Metabolic Profiling Reveals Significant Perturbations of Intracellular Glucose Homeostasis in Enterovirus-Infected Cells.


ABSTRACT: Enterovirus A71 (EV-A71) is a common cause of hand, foot, and mouth disease. Severe EV-A71 infections may be associated with life-threatening neurological complications. However, the pathogenic mechanisms underlying these severe clinical and pathological features remain incompletely understood. Metabolites are known to play critical roles in multiple stages of the replication cycles of viruses. The metabolic reprogramming induced by viral infections is essential for optimal virus replication and may be potential antiviral targets. In this study, we applied targeted metabolomics profiling to investigate the metabolic changes of induced pluripotent human stem cell (iPSC)-derived neural progenitor cells (NPCs) upon EV-A71 infection. A targeted quantitation of polar metabolites identified 14 candidates with altered expression profiles. A pathway enrichment analysis pinpointed glucose metabolic pathways as being highly perturbed upon EV-A71 infection. Gene silencing of one of the key enzymes of glycolysis, 6-phosphofructo-2-kinase (PFKFB3), significantly suppressed EV-A71 replication in vitro. Collectively, we demonstrated the feasibility to manipulate EV-A71-triggered host metabolic reprogramming as a potential anti-EV-A71 strategy.

SUBMITTER: Zou Z 

PROVIDER: S-EPMC7466099 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Metabolic Profiling Reveals Significant Perturbations of Intracellular Glucose Homeostasis in <i>Enterovirus</i>-Infected Cells.

Zou Zijiao Z   Tsang Jessica Oi-Ling JO   Yan Bingpeng B   Chik Kenn Ka-Heng KK   Chan Chris Chun-Yiu CC   Cao Jianli J   Liang Ronghui R   Tang Kaiming K   Yin Feifei F   Ye Zi-Wei ZW   Chu Hin H   Chan Jasper Fuk-Woo JF   Yuan Shuofeng S   Yuen Kwok-Yung KY  

Metabolites 20200723 8


<i>Enterovirus</i> A71 (EV-A71) is a common cause of hand, foot, and mouth disease. Severe EV-A71 infections may be associated with life-threatening neurological complications. However, the pathogenic mechanisms underlying these severe clinical and pathological features remain incompletely understood. Metabolites are known to play critical roles in multiple stages of the replication cycles of viruses. The metabolic reprogramming induced by viral infections is essential for optimal virus replicat  ...[more]

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