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Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling.
- Source :
-
PLoS pathogens [PLoS Pathog] 2020 Jun 09; Vol. 16 (6), pp. e1008568. Date of Electronic Publication: 2020 Jun 09 (Print Publication: 2020). - 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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Cell Line
DNA Replication drug effects
DNA, Viral biosynthesis
Deoxyglucose pharmacology
Glucose metabolism
Humans
Lactic Acid metabolism
Mechanistic Target of Rapamycin Complex 1 metabolism
Proto-Oncogene Proteins c-akt metabolism
Roseolovirus Infections drug therapy
Roseolovirus Infections pathology
T-Lymphocytes pathology
T-Lymphocytes virology
Viral Proteins biosynthesis
Virion metabolism
Glycolysis
Herpesvirus 6, Human metabolism
Roseolovirus Infections metabolism
Signal Transduction
T-Lymphocytes metabolism
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 16
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 32516328
- Full Text :
- https://doi.org/10.1371/journal.ppat.1008568