Lyssavirus matrix protein stabilizes RGS4 to suppress ferroptosis via incomplete autophagy and iron metabolic reprogramming.

Lyssavirus M protein stabilizes RGS4 to suppress ferroptosis by inhibiting ferritinophagy through incomplete autophagy, facilitating viral replication.

• Why it matters: Understanding how lyssavirus evades host immune responses is crucial for developing targeted therapies, as ferroptosis plays a key role in antiviral defense mechanisms.
• What they did: The study examined the RGS4-HERC2-NCOA4-FTH pathway in RABV-infected cells, revealing that the M protein prevents RGS4 degradation via incomplete autophagy, maintaining ferroptosis suppression.
• The result: This mechanism highlights a lyssavirus-specific regulatory axis that modulates ferroptosis, emphasizing ferroptosis's role in infection and pathogenesis, and may inform future antiviral strategies.