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Updated: May 22, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
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Aggregatin is a mitochondrial regulator of MAVS activation to drive innate immunity

Ju Gao1, Mao Ding1, Yanbin Xiyang1

  • 1Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, United States.

Journal of Immunology (Baltimore, Md. : 1950)
|March 12, 2025
PubMed

Insights

Aggregatin protein initiates mitochondrial antiviral-signaling protein (MAVS) aggregation, crucial for antiviral immunity. This discovery reveals Aggregatin

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Mitochondrial antiviral-signaling protein (MAVS) aggregation on mitochondria is essential for activating type I interferon (IFN-I) antiviral responses.
  • The specific mitochondrial factor regulating MAVS aggregation has remained unidentified.

Purpose of the Study:

  • To identify the mitochondrial factor responsible for MAVS aggregation and investigate its role in innate immunity.
  • To elucidate the mechanism by which Aggregatin regulates MAVS aggregation and antiviral signaling.

Main Methods:

  • Cellular localization studies of Aggregatin.
  • Induction of MAVS aggregation and IFN-I responses in HEK293 and THP-1 cells.
  • Viral infection models and Aggregatin knockout experiments.
  • Identification of Nemo-like kinase as a regulator of Aggregatin phosphorylation.

Main Results:

  • Aggregatin is localized to mitochondria and can independently induce MAVS aggregation and IFN-I responses.
  • Mitochondrial Aggregatin levels increase upon viral infection.
  • Aggregatin knockout significantly impairs viral infection-induced MAVS aggregation and IFN-I signaling.
  • Nemo-like kinase phosphorylates Aggregatin at Ser59, modulating its stability and cross-seeding activity.

Conclusions:

  • Aggregatin acts as a critical cross-seeding factor for MAVS aggregation on mitochondria, thereby orchestrating innate immune signaling.
  • Aggregatin plays a vital physiological role in innate immunity against viral infections.
Keywords:
AggregatinMAVSinnate immunityinterferonmitochondriaviral infection

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