PNMA4 enhances anti-RNA virus immunity by promoting RIG-I signaling pathway

Area of Science:

• Immunology
• Cell Biology
• Virology

Background:

• Mitochondria are central to innate immune signaling.
• Mitochondrial antiviral signaling protein (MAVS) is critical for interferon-β (IFN-β) production and antiviral responses.
• MAVS initiates innate antiviral defenses against RNA viruses.

Purpose of the Study:

• To identify novel MAVS-interacting proteins involved in innate antiviral immunity.
• To elucidate the role of Paraneoplastic Ma Family 4 (PNMA4/MOAP1) in the retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) signaling pathway.

Main Methods:

• Proximity-based labeling technology in THP-1 cells to identify MAVS interactors.
• Investigating the effect of PNMA4 absence on RNA virus-induced antiviral pathway activation in Pnma4^-/- mice and cell models.

Main Results:

• PNMA4 was identified as a MAVS-interacting protein that enhances RLR signaling.
• Absence of PNMA4 significantly reduced RNA virus-induced antiviral pathway activation.
• Pnma4^-/- mice exhibited increased susceptibility to viral infections.
• PNMA4 enhances RIG-I and MAVS interaction post-RNA virus infection.
• PNMA4 facilitates TRIM25-mediated RIG-I K63-linked polyubiquitination at K657.

Conclusions:

• PNMA4 is a positive regulator of innate antiviral responses.
• PNMA4 enhances antiviral immunity by promoting RIG-I activation and signaling.
• PNMA4 plays a significant role in host defense against RNA viruses.