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Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling.
- Source :
- PLoS Pathogens; 6/9/2020, Vol. 16 Issue 6, p1-23, 23p
- Publication Year :
- 2020
-
Abstract
- 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. Author summary: Human herpesvirus 6 (HHV-6) is a member of the betaherpesvirinae family, which primarily infects T lymphocytes. In the study presented here, we have demonstrated that HHV-6A infection promotes glucose metabolism in infected T cells. Further exploration into the mechanism demonstrated that HHV-6A infection increases the expressions of the key glucose transporters and glycolytic enzymes, as well as activates the AKT-mTORC1 signaling, which is involved in HHV-6A-induced glycolysis activation in HHV-6-infected T cells. Importantly, suppression of glycolysis or mTORC1 activity effectively reduced HHV-6A propagation. Therefore, recognition of the effects of HHV-6 on host cell metabolism will not only facilitate a better understanding of viral pathogenesis but also could reveal potential therapeutic targets for HHV-6-associated diseases by metabolic manipulation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 16
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 143681005
- Full Text :
- https://doi.org/10.1371/journal.ppat.1008568