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.
Highlights
Enteroviruses are non-enveloped, single-stranded, positive sense RNA viruses which belong to the genus Enterovirus in the family Picornaviridae [1]
To investigate the pathogenesis of Enterovirus A71 (EV-A71)-associated neurological manifestations, we first exploited Human neural progenitor cells (hNPCs) to establish an in vitro model for the characterization of the metabolic changes induced by an EV-A71 infection
These findings suggest that hNPCs were highly susceptible to an EV-A71 infection
Summary
Enteroviruses are non-enveloped, single-stranded, positive sense RNA viruses which belong to the genus Enterovirus in the family Picornaviridae [1]. The genus Enterovirus contains 15 species, including. Outbreaks of HFMD have been reported worldwide. In mainland China, around 13 million HFMD cases were reported between 2008 and 2015, including at least 123,261 severe cases and 3322 deaths [3]. Severe EV-A71 infections can progress to serious neurological complications, including aseptic meningitis, poliomyelitis-like acute flaccid paralysis, brainstem encephalitis, and non-cardiogenic pulmonary edema [4]. The pathogenesis underlying these clinical features is not fully understood
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