NLRP3 inflammasome and Epstein-Barr virus: mutual regulation and therapeutic potential

Epstein-Barr virus (EBV), a prevalent and virulent human γ-herpesvirus, is etiologically linked to an extensive spectrum of malignancies and autoimmune disorders. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome serves as a central sensor of innate immune defense and critically modulates host-EBV crosstalk. Nonetheless, current studies mostly concentrate on individual regulatory events or specific hematological malignancies. A systematic and holistic depiction of the full bidirectional regulatory network between EBV and the NLRP3 inflammasome remains lacking. In addition, contradictory findings across different experimental models and the inherent drawbacks of existing research systems have not been objectively interpreted, which hinders a thorough understanding of this regulatory axis. Therefore, we systematically summarize the dual regulatory molecular pathways between EBV and the NLRP3 inflammasome, integrate the latest cellular and molecular mechanisms reported in recent years, critically discuss prevailing controversies and limitations in relevant research, and further explore the translational potential of NLRP3 as a therapeutic target. This review intends to refine the theoretical framework of EBV-driven tumorigenesis and immune dysfunction, and offer novel insights for future mechanistic investigations and clinical targeted therapy.