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Updated: Jun 28, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
AMPK restricts HHV-6A replication by inhibiting glycolysis and mTOR signaling
Xiaodi Yang1, Siyu Tian1, Zhujiang Min1
1Department of Medical Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
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.
Insights
AMP-activated protein kinase (AMPK) regulates cellular energy. Activating AMPK combats human herpesvirus 6A (HHV-6A) infection by inhibiting viral propagation and replication, highlighting AMPK as a potential antiviral target.
Area of Science:
- Cellular biology
- Virology
- Metabolism
Background:
- AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolic homeostasis.
- Human herpesvirus 6A (HHV-6A) is a significant human pathogen.
- The interplay between AMPK and HHV-6A infection is not well understood.
Purpose of the Study:
- To investigate the role of AMPK in response to HHV-6A infection.
- To explore the therapeutic potential of targeting AMPK against HHV-6A.
Main Methods:
- Investigated AMPK phosphorylation status in HHV-6A infected T cells.
- Utilized pharmacological AMPK activators (AICAR, metformin) to assess their impact on viral propagation.
- Analyzed effects on glycolysis, glucose metabolism, and mTOR signaling.
- Assessed viral DNA replication and virion production in infected cells.
Main Results:
- HHV-6A infection significantly downregulated active AMPK in T cells.
- AMPK activation by AICAR and metformin attenuated HHV-6A propagation and replication.
- AMPK activation inhibited HHV-6A-induced glycolysis, glucose metabolism, and lactate secretion.
- AMPK activation led to mTOR signaling inactivation and reduced viral DNA and virion production.
Conclusions:
- AMPK activity is suppressed during HHV-6A infection.
- Pharmacological activation of AMPK demonstrates potent antiviral effects against HHV-6A.
- AMPK represents a promising therapeutic target for managing HHV-6A infections.
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