Decoding phosphoinositide signaling in viral pathogenesis and autoimmune disorders

Phosphoinositide (PIP) lipids are master regulators of cellular signaling, membrane dynamics, and trafficking. Dysregulation of PIP signaling contributes critically to autoimmune disorders, where it disrupts immune tolerance and promotes inflammatory tissue damage. Similarly, viruses extensively exploit host PIP signaling pathways for entry, replication, and immune evasion. However, a comprehensive analysis linking PIP dysregulation across specific viral infections to autoimmune mechanisms is lacking. This review bridges this gap by decoding the intricate roles of PIP signaling in both viral pathogenesis and autoimmunity. We detail how eight distinct viral pathogens manipulate PIP networks and explore the resulting implications for autoimmune initiation or exacerbation. We synthesize findings on key PIP species, their effector proteins, and the modulated immune pathways central to both disease contexts. By elucidating these shared and unique mechanisms, this review identifies promising PIP-centric targets for therapeutic intervention in viral diseases and autoimmune disorders.