Beta Interferon Regulation of Glucose Metabolism Is PI3K/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3

Burke, J. D.; Platanias, Leonidas C.; Fish, Eleanor N.

doi:10.1128/jvi.02649-13

Cited by 71 publications

(70 citation statements)

References 99 publications

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“…As IFN-β has been shown to directly regulate glucose metabolism (26), it seemed possible that viral-induced glycolysis in pDCs could be mediated by IFN-α/β. To test this, we exposed pDCs to IFN-α and measured 13 C-lactate production.…”

Section: Resultsmentioning

confidence: 99%

Cutting Edge: Critical Role of Glycolysis in Human Plasmacytoid Dendritic Cell Antiviral Responses

Bajwa

DeBerardinis

Shao

et al. 2016

The Journal of Immunology

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Plasmacytoid dendritic cells (pDCs) are vital to antiviral defense, directing immune responses via secretion of huge concentrations of IFN-α. These cells are critical in protecting the lung against clinically relevant respiratory viruses, particularly influenza (Flu), a virus responsible for substantial worldwide morbidity and mortality. How pDC responses to such viral pathogens are regulated, however, is poorly understood in humans. Using an unbiased approach of gene chip analysis, we discovered that Flu significantly impacts metabolism in primary human pDCs. We demonstrate that Flu and RV, another common respiratory virus, induce glycolysis in pDCs and that this metabolic pathway regulates pDC antiviral functions including IFN-α production and phenotypic maturation. Intranasal vaccination of human volunteers with live influenza virus also increases glycolysis in circulating pDCs, highlighting a previously unrecognized potential role for metabolism in regulating pDC immune responses to viral infections in humans.

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Section: Resultsmentioning

confidence: 99%

Cutting Edge: Critical Role of Glycolysis in Human Plasmacytoid Dendritic Cell Antiviral Responses

Bajwa

DeBerardinis

Shao

et al. 2016

The Journal of Immunology

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“…The purpose and mechanism underlying this observation remains to be elucidated. The precise mechanism whereby IFN signaling converges with glucose utilization programs also remains to be fully resolved, but recent studies demonstrated that interferon signaling leads to changes in glucose uptake, which is important for the antiviral response (Burke et al, 2014). Thus, whereas alternative fuel substrate availability is coupled to and necessary for adaptation to bacterial inflammation, glucose availability is coupled to and necessary for cellular adaptation to viral inflammation.…”

Section: Discussionmentioning

confidence: 99%

Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation

Wang

Huen

Luan

et al. 2016

Cell

465

467

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Summary Acute infections are associated with a set of stereotypic behavioral responses, including anorexia, lethargy, and social withdrawal. Although these so called sickness behaviors are the most common and familiar symptoms of infections, their roles in host defense are largely unknown. Here we investigated the role of anorexia in models of bacterial and viral infections. We found that anorexia was protective while nutritional supplementation was detrimental in bacterial sepsis. Furthermore, glucose was necessary and sufficient for these effects. In contrast, nutritional supplementation protected against mortality from influenza infection and viral sepsis, while blocking glucose utilization was lethal. In both bacterial and viral models, these effects were largely independent of pathogen load and magnitude of inflammation. Instead, we identify opposing metabolic requirements tied to cellular stress adaptations critical for tolerance of differential inflammatory states.

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“…For example, IFNβ stimulates a PI3K/AKT-dependent glucose uptake in mouse embryonic fibroblasts that may enhance ATP production (32). Inhibition of IFNβ-induced glycolysis with 2-deoxyglucose (2-DG), a competitive inhibitor of hexokinase, the first enzyme in the glycolysis cascade, enhances replication of coxsackievirus B3 in vitro (32). This suggests that enhanced glycolysis may support the establishment of an antiviral state.…”

Section: Effects Of Ifns On Energy Metabolismmentioning

confidence: 99%

Effects of Interferons and Viruses on Metabolism

2016

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Interferons (IFNs) are potent pleiotropic cytokines that broadly alter cellular functions in response to viral and other infections. These alterations include changes in protein synthesis, proliferation, membrane composition, and the nutritional microenvironment. Recent evidence suggests that antiviral responses are supported by an IFN-induced rewiring of the cellular metabolism. In this review, we discuss the roles of type I and type II IFNs in regulating the cellular metabolism and biosynthetic reactions. Furthermore, we give an overview of how viruses themselves affect these metabolic activities to promote their replication. In addition, we focus on the lipid as well as amino acid metabolisms, through which IFNs exert potent antiviral and immunomodulatory activities. Conversely, the expression of IFNs is controlled by the nutrient sensor mammalian target of rapamycin or by direct reprograming of lipid metabolic pathways. These findings establish a mutual relationship between IFN production and metabolic core processes.

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Beta Interferon Regulation of Glucose Metabolism Is PI3K/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3

Abstract: An effective type I interferon (IFN)-

Cited by 71 publications

References 99 publications

Cutting Edge: Critical Role of Glycolysis in Human Plasmacytoid Dendritic Cell Antiviral Responses

Cutting Edge: Critical Role of Glycolysis in Human Plasmacytoid Dendritic Cell Antiviral Responses

Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation

Effects of Interferons and Viruses on Metabolism

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