TRIM23 mediates cGAS-induced autophagy in anti-HSV defense

Area of Science:

• Immunology
• Cellular Biology
• Virology

Background:

• The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is known to induce interferon responses.
• The mechanisms by which cGAS-STING signaling triggers autophagy remain less understood.
• Autophagy plays a critical role in cellular defense against viral infections.

Purpose of the Study:

• To elucidate the role of TRIM23 in cGAS-STING-mediated autophagy during viral infections.
• To identify the molecular mediators linking cGAS-STING activation to autophagy induction.
• To investigate the therapeutic potential of the cGAS-STING-TBK1-TRIM23 axis.

Main Methods:

• Genetic ablation of TRIM23 in cells.
• Herpes Simplex Virus 1 (HSV-1) infection models.
• Analysis of TRIM23 phosphorylation and autoubiquitination.
• Functional assays using patient-derived fibroblasts with TBK1 mutations.

Main Results:

• TRIM23 is essential for cGAS-STING-dependent antiviral autophagy.
• TRIM23 genetic deletion impairs autophagic control of HSV-1.
• TBK1-mediated phosphorylation of TRIM23 at S39 is required for autophagy induction.
• Patient-derived cells with TBK1 mutations show defective TRIM23-mediated autophagy.

Conclusions:

• The cGAS-STING-TBK1-TRIM23 signaling axis is identified as a critical pathway for inducing autophagy and antiviral defense.
• TRIM23 acts as a key mediator linking cGAS-STING activation to autophagy.
• This pathway represents a potential target for developing novel therapeutic strategies against viral and inflammatory diseases.