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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2023

Open Access 01-12-2023 | Research

Glycolytic shift during West Nile virus infection provides new therapeutic opportunities

Authors: Patricia Mingo-Casas, Ana-Belén Blázquez, Marta Gómez de Cedrón, Ana San-Félix, Susana Molina, Estela Escribano-Romero, Eva Calvo-Pinilla, Nereida Jiménez de Oya, Ana Ramírez de Molina, Juan-Carlos Saiz, María-Jesús Pérez-Pérez, Miguel A. Martín-Acebes

Published in: Journal of Neuroinflammation | Issue 1/2023

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Abstract

Background

Viral rewiring of host bioenergetics and immunometabolism may provide novel targets for therapeutic interventions against viral infections. Here, we have explored the effect on bioenergetics during the infection with the mosquito-borne flavivirus West Nile virus (WNV), a medically relevant neurotropic pathogen causing outbreaks of meningitis and encephalitis worldwide.

Results

A systematic literature search and meta-analysis pointed to a misbalance of glucose homeostasis in the central nervous system of WNV patients. Real-time bioenergetic analyses confirmed upregulation of aerobic glycolysis and a reduction of mitochondrial oxidative phosphorylation during viral replication in cultured cells. Transcriptomics analyses in neural tissues from experimentally infected mice unveiled a glycolytic shift including the upregulation of hexokinases 2 and 3 (Hk2 and Hk3) and pyruvate dehydrogenase kinase 4 (Pdk4). Treatment of infected mice with the Hk inhibitor, 2-deoxy-D-glucose, or the Pdk4 inhibitor, dichloroacetate, alleviated WNV-induced neuroinflammation.

Conclusions

These results highlight the importance of host energetic metabolism and specifically glycolysis in WNV infection in vivo. This study provides proof of concept for the druggability of the glycolytic pathway for the future development of therapies to combat WNV pathology.
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Metadata
Title
Glycolytic shift during West Nile virus infection provides new therapeutic opportunities
Authors
Patricia Mingo-Casas
Ana-Belén Blázquez
Marta Gómez de Cedrón
Ana San-Félix
Susana Molina
Estela Escribano-Romero
Eva Calvo-Pinilla
Nereida Jiménez de Oya
Ana Ramírez de Molina
Juan-Carlos Saiz
María-Jesús Pérez-Pérez
Miguel A. Martín-Acebes
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-023-02899-3

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