Rhinovirus induces an anabolic reprogramming in host cell metabolism essential for viral replication

Rhinoviruses (RVs) are responsible for the majority of upper airway infections; despite their high prevalence and the resulting economic burden, effective treatment is lacking. We report here that RV induces metabolic alterations in host cells, which offer an efficient target for antiviral intervent...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-07, Vol.115 (30), p.E7158-E7165
Main Authors: Gualdoni, Guido A., Mayer, Katharina A., Kapsch, Anna-Maria, Kreuzberg, Katharina, Puck, Alexander, Kienzl, Philip, Oberndorfer, Felicitas, Frühwirth, Karin, Winkler, Stefan, Blaas, Dieter, Zlabinger, Gerhard J., Stöckl, Johannes
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Animal models
Animals
Antiviral drugs
Biological Sciences
Cells
Deoxyglucose
Deoxyglucose - pharmacology
Deprivation
Female
Glucose
Glucose transporter
Glucose Transporter Type 1 - genetics
Glucose Transporter Type 1 - metabolism
Glycolysis
Infections
Intervention
Lipogenesis
Lipogenesis - drug effects
Lipogenesis - genetics
Metabolism
Metabolomics
Mice
Nucleotides - biosynthesis
Nucleotides - genetics
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Picornaviridae Infections - drug therapy
Picornaviridae Infections - genetics
Picornaviridae Infections - metabolism
Picornaviridae Infections - pathology
PNAS Plus
Replication
Respiratory tract
Rhinovirus
Rhinovirus - physiology
Target recognition
Viral infections
Virus Replication - drug effects
Virus Replication - physiology
Viruses
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Summary:Rhinoviruses (RVs) are responsible for the majority of upper airway infections; despite their high prevalence and the resulting economic burden, effective treatment is lacking. We report here that RV induces metabolic alterations in host cells, which offer an efficient target for antiviral intervention. We show that RV-infected cells rapidly up-regulate glucose uptake in a PI3K-dependent manner. In parallel, infected cells enhance the expression of the PI3K-regulated glucose transporter GLUT1. In-depth metabolomic analysis of RV-infected cells revealed a critical role of glucose mobilization from extracellular and intracellular pools via glycogenolysis for viral replication. Infection resulted in a highly anabolic state, including enhanced nucleotide synthesis and lipogenesis. Consistently, we observed that glucose deprivation from medium and via glycolysis inhibition by 2-deoxyglucose (2-DG) potently impairs viral replication. Metabolomic analysis showed that 2-DG specifically reverts the RV-induced anabolic reprogramming. In addition, treatment with 2-DG inhibited RV infection and inflammation in a murine model. Thus, we demonstrate that the specific metabolic fingerprint of RV infection can be used to identify new targets for therapeutic intervention.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1800525115