Related Experiment Video

Updated: Sep 9, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

10.6K

Manganese mediates antiviral effects by driving an ATM -TBK1 phosphorylation signaling pathway

Hongyan Sui1, Rosana Wiscovitch-Russo1, Silvia Cachaco1

  • 1Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory, Frederick, MD, 21702.

Biorxiv : the Preprint Server for Biology
|September 2, 2025
PubMed

Insights

Manganese (Mn) activates cytoplasmic ATM and TBK1, enhancing innate immunity against viral infections like HIV. This discovery suggests Mn supplementation as a potential antiviral therapy.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Manganese (Mn) was previously shown to enhance innate immune responses to viral infections.
  • The precise mechanism by which Mn induces TANK-binding kinase 1 (TBK1) phosphorylation remained unclear.

Purpose of the Study:

  • To elucidate the mechanism underlying Mn-induced TBK1 phosphorylation.
  • To investigate the role of Ataxia-telangiectasia mutated (ATM) in this process.
  • To explore the potential of Mn as an antiviral therapeutic.

Main Methods:

  • Investigated Mn-induced TBK1 phosphorylation in various cell lines and primary human immune cells.
  • Utilized ATM-deficient cells to assess ATM's role.
  • Performed immunoprecipitation assays to examine ATM and TBK1 interactions and phosphorylation.
  • Quantified HIV replication and antiviral cytokine production.

Main Results:

  • Mn dose-dependently induced TBK1 phosphorylation in an ATM-dependent manner, mediated by cytoplasmic ATM.
  • Mn promoted ATM phosphorylation at specific sites (Ser1893, Ser1981, Ser2996).
  • Mn induced dissociation of TBK1 from ATM upon phosphorylation, correlating with enhanced antiviral cytokine production and suppressed HIV replication.

Conclusions:

  • A cytoplasmic ATM-TBK1 phosphorylation cycle is identified as a critical regulator of antiviral innate immunity.
  • Mn supplementation shows potential as a therapeutic strategy against HIV and other viral infections.

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