Regulation of VISA/MAVS Signalosome Dynamics and Immune Homeostasis.

VISA/MAVS is a central signaling hub that links viral RNA sensing to type I interferon production and inflammatory responses. Because of its potent signal-amplifying capacity, VISA activity must be precisely controlled: insufficient activation compromises antiviral defense, whereas excessive or spontaneous activation can drive chronic inflammation and autoimmune disease. Recent studies have revealed a complex regulatory network governing VISA signaling, involving post-translational modifications, dynamic protein interactions, selective degradation pathways, metabolic cues, and intrinsic inhibitory mechanisms that collectively determine its activation threshold, signaling duration, and downstream output. In this review, we discuss the molecular mechanisms that regulate VISA activation, signal propagation, signal termination, and quiescence maintenance under resting conditions. We propose that immune homeostasis is achieved not through a simple on-off switch, but through continuous regulation of the VISA signalosome life cycle. This framework provides an integrated view of VISA and offers new insights into the molecular mechanisms underlying immune homeostasis.