1. AMPK restricts HHV-6A replication by inhibiting glycolysis and mTOR signaling.
- Author
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Yang X, Tian S, Min Z, Garbarino E, Ma J, Jia J, Tang H, and Li L
- Subjects
- Humans, Aminoimidazole Carboxamide analogs & derivatives, Aminoimidazole Carboxamide pharmacology, Roseolovirus Infections virology, Roseolovirus Infections metabolism, Metformin pharmacology, Ribonucleotides pharmacology, Phosphorylation, Herpesvirus 6, Human physiology, Herpesvirus 6, Human genetics, Herpesvirus 6, Human metabolism, Virus Replication drug effects, Glycolysis, TOR Serine-Threonine Kinases metabolism, TOR Serine-Threonine Kinases genetics, AMP-Activated Protein Kinases metabolism, AMP-Activated Protein Kinases genetics, Signal Transduction
- Abstract
AMP-activated protein kinase (AMPK) is a cellular energy sensor regulating metabolic homeostasis. In this study, we investigated the role of AMPK in response to human herpesvirus 6A (HHV-6A) infection. We show that HHV-6A infection significantly downregulates the active phosphorylated state of AMPK in infected T cells. Pharmacological activation of AMPK highly attenuated HHV-6A propagation. Mechanistically, we found that the activation of AMPK by AICAR blocked HHV-6-induced glycolysis by inhibiting glucose metabolism and lactate secretion, as well as decreasing expressions of key glucose transporters and glycolytic enzymes. In addition, mTOR signaling has been inactivated in HHV-6A infected T cells by AICAR treatment. We also showed that HHV-6A infection of human umbilical cord blood mononuclear cells (CBMCs) reduced AMPK activity whereas the activation of AMPK by metformin drastically reduced HHV-6A DNA replication and virions production. Taken together, this study demonstrates that AMPK is a promising antiviral therapeutic target against HHV-6A infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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