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.

Virology
|April 17, 2024
PubMed

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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