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Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling

Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus worldwide. However, whether and how HHV-6 infection influences the metabolic machinery of the host cell to provide the energy and biosynthetic resources for virus propagation remains unknown. In this study, we i...

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Autores principales: Wu, Zhisheng, Jia, Junli, Xu, Xianyi, Xu, Mengyuan, Peng, Guangyong, Ma, Jingjing, Jiang, Xuefeng, Yao, Jialin, Yao, Kun, Li, Lingyun, Tang, Huamin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282626/
https://www.ncbi.nlm.nih.gov/pubmed/32516328
http://dx.doi.org/10.1371/journal.ppat.1008568
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author Wu, Zhisheng
Jia, Junli
Xu, Xianyi
Xu, Mengyuan
Peng, Guangyong
Ma, Jingjing
Jiang, Xuefeng
Yao, Jialin
Yao, Kun
Li, Lingyun
Tang, Huamin
author_facet Wu, Zhisheng
Jia, Junli
Xu, Xianyi
Xu, Mengyuan
Peng, Guangyong
Ma, Jingjing
Jiang, Xuefeng
Yao, Jialin
Yao, Kun
Li, Lingyun
Tang, Huamin
author_sort Wu, Zhisheng
collection PubMed
description Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus worldwide. However, whether and how HHV-6 infection influences the metabolic machinery of the host cell to provide the energy and biosynthetic resources for virus propagation remains unknown. In this study, we identified that HHV-6A infection promotes glucose metabolism in infected T cells, resulting in elevated glycolytic activity with an increase of glucose uptake, glucose consumption and lactate secretion. Furthermore, we explored the mechanisms involved in HHV-6A-mediated glycolytic activation in the infected T cells. We found increased expressions of the key glucose transporters and glycolytic enzymes in HHV-6A-infected T cells. In addition, HHV-6A infection dramatically activated AKT-mTORC1 signaling in the infected T cells and pharmacological inhibition of mTORC1 blocked HHV-6A-mediated glycolytic activation. We also found that direct inhibition of glycolysis by 2-Deoxy-D-glucose (2-DG) or inhibition of mTORC1 activity in HHV-6A-infected T cells effectively reduced HHV-6 DNA replication, protein synthesis and virion production. These results not only reveal the mechanism of how HHV-6 infection affects host cell metabolism, but also suggest that targeting the metabolic pathway could be a new avenue for HHV-6 therapy.
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spelling pubmed-72826262020-06-17 Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling Wu, Zhisheng Jia, Junli Xu, Xianyi Xu, Mengyuan Peng, Guangyong Ma, Jingjing Jiang, Xuefeng Yao, Jialin Yao, Kun Li, Lingyun Tang, Huamin PLoS Pathog Research Article Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus worldwide. However, whether and how HHV-6 infection influences the metabolic machinery of the host cell to provide the energy and biosynthetic resources for virus propagation remains unknown. In this study, we identified that HHV-6A infection promotes glucose metabolism in infected T cells, resulting in elevated glycolytic activity with an increase of glucose uptake, glucose consumption and lactate secretion. Furthermore, we explored the mechanisms involved in HHV-6A-mediated glycolytic activation in the infected T cells. We found increased expressions of the key glucose transporters and glycolytic enzymes in HHV-6A-infected T cells. In addition, HHV-6A infection dramatically activated AKT-mTORC1 signaling in the infected T cells and pharmacological inhibition of mTORC1 blocked HHV-6A-mediated glycolytic activation. We also found that direct inhibition of glycolysis by 2-Deoxy-D-glucose (2-DG) or inhibition of mTORC1 activity in HHV-6A-infected T cells effectively reduced HHV-6 DNA replication, protein synthesis and virion production. These results not only reveal the mechanism of how HHV-6 infection affects host cell metabolism, but also suggest that targeting the metabolic pathway could be a new avenue for HHV-6 therapy. Public Library of Science 2020-06-09 /pmc/articles/PMC7282626/ /pubmed/32516328 http://dx.doi.org/10.1371/journal.ppat.1008568 Text en © 2020 Wu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wu, Zhisheng
Jia, Junli
Xu, Xianyi
Xu, Mengyuan
Peng, Guangyong
Ma, Jingjing
Jiang, Xuefeng
Yao, Jialin
Yao, Kun
Li, Lingyun
Tang, Huamin
Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling
title Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling
title_full Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling
title_fullStr Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling
title_full_unstemmed Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling
title_short Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling
title_sort human herpesvirus 6a promotes glycolysis in infected t cells by activation of mtor signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282626/
https://www.ncbi.nlm.nih.gov/pubmed/32516328
http://dx.doi.org/10.1371/journal.ppat.1008568
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