Metabolomic Insights into Human Arboviral Infections: Dengue, Chikungunya, and Zika Viruses

Byers, Nathaniel M.; Fleshman, Amy C.; Perera, Rushika; Molins, Claudia R.

doi:10.3390/v11030225

Cited by 42 publications

(34 citation statements)

References 137 publications

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“…Surprisingly, only limited similarity was found in the metabolic profile between the two infected cell lines during the course of infection and in relation to uninfected cells. Thus, although it has been reported that viruses belonging to different families could cause some common metabolic responses [23,24], in our study it was observed that CrPV could induce only minimal common metabolic changes in different host cells.…”

Section: Discussioncontrasting

confidence: 69%

Metabolomic Analysis of Cricket paralysis virus Infection in Drosophila S2 Cells Reveals Divergent Effects on Central Carbon Metabolism as Compared with Silkworm Bm5 Cells

Wang

Swevers

Meulebroek

et al. 2020

Viruses

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High-throughput approaches have opened new opportunities for understanding biological processes such as persistent virus infections, which are widespread. However, the potential of persistent infections to develop towards pathogenesis remains to be investigated, particularly with respect to the role of host metabolism. To explore the interactions between cellular metabolism and persistent/pathogenic virus infection, we performed untargeted and targeted metabolomic analysis to examine the effects of Cricket paralysis virus (CrPV, Dicistroviridae) in persistently infected silkworm Bm5 cells and acutely infected Drosophila S2 cells. Our previous study (Viruses 2019, 11, 861) established that both glucose and glutamine levels significantly increased during the persistent period of CrPV infection of Bm5 cells, while they decreased steeply during the pathogenic stages. Strikingly, in this study, an almost opposite pattern in change of metabolites was observed during different stages of acute infection of S2 cells. More specifically, a significant decrease in amino acids and carbohydrates was observed prior to pathogenesis, while their abundance significantly increased again during pathogenesis. Our study illustrates the occurrence of diametrically opposite changes in central carbon mechanisms during CrPV infection of S2 and Bm5 cells that is possibly related to the type of infection (acute or persistent) that is triggered by the virus.

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Section: Discussioncontrasting

confidence: 69%

Metabolomic Analysis of Cricket paralysis virus Infection in Drosophila S2 Cells Reveals Divergent Effects on Central Carbon Metabolism as Compared with Silkworm Bm5 Cells

Wang

Swevers

Meulebroek

et al. 2020

Viruses

View full text Add to dashboard Cite

show abstract

“…Viruses are obligate intracellular microorganisms that induce the reprograming of the host cell metabolism to support their own replication. This has been previously reported for various viruses, including HCMV [15], Middle East respiratory syndrome coronavirus (MERS-CoV) [16,17], adenovirus [18], dengue virus, and Zika virus [19]. For example, HCMV-infected cells display an increased dependence on glucose, and upregulate their glycolysis and lactate production.…”

Section: Discussionsupporting

confidence: 57%

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

et al. 2020

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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.

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“…This valuable information has unveiled potential antiviral targets that are now starting to be explored. It is expected that the detailed knowledge of the metabolic alterations (e.g., lipid metabolism) during ZIKV and other arboviral infections could help to design novel therapeutics, but also be useful to the identification of molecular biomarkers suitable for improved diagnostic [12]. This review summarizes the principal findings and the current status on the progress of the development of drugs that interfere with lipid metabolism and function as antivirals against ZIKV.…”

Section: Introductionmentioning

confidence: 99%

Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses

2019

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The Zika virus (ZIKV) is a mosquito-borne flavivirus that can lead to birth defects (microcephaly), ocular lesions and neurological disorders (Guillain-Barré syndrome). There is no licensed vaccine or antiviral treatment against ZIKV infection. The effort to understand the complex interactions of ZIKV with cellular networks contributes to the identification of novel host-directed antiviral (HDA) candidates. Among the cellular pathways involved in infection, lipid metabolism gains attention. In ZIKV-infected cells lipid metabolism attributed to intracellular membrane remodeling, virion morphogenesis, autophagy modulation, innate immunity and inflammation. The key roles played by the cellular structures associated with lipid metabolism, such as peroxisomes and lipid droplets, are starting to be deciphered. Consequently, there is a wide variety of lipid-related antiviral strategies that are currently under consideration, which include an inhibition of sterol regulatory element-binding proteins (SREBP), the activation of adenosine-monophosphate activated kinase (AMPK), an inhibition of acetyl-Coenzyme A carboxylase (ACC), interference with sphingolipid metabolism, blockage of intracellular cholesterol trafficking, or a treatment with cholesterol derivatives. Remarkably, most of the HDAs identified in these studies are also effective against flaviviruses other than ZIKV (West Nile virus and dengue virus), supporting their broad-spectrum effect. Considering that lipid metabolism is one of the main cellular pathways suitable for pharmacological intervention, the idea of repositioning drugs targeting lipid metabolism as antiviral candidates is gaining force.

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Metabolomic Insights into Human Arboviral Infections: Dengue, Chikungunya, and Zika Viruses

Cited by 42 publications

References 137 publications

Metabolomic Analysis of Cricket paralysis virus Infection in Drosophila S2 Cells Reveals Divergent Effects on Central Carbon Metabolism as Compared with Silkworm Bm5 Cells

Metabolomic Analysis of Cricket paralysis virus Infection in Drosophila S2 Cells Reveals Divergent Effects on Central Carbon Metabolism as Compared with Silkworm Bm5 Cells

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

Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses

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