African swine fever virus pEP364R acts as an important inflammatory-inducing factor to activate NLRP3 inflammasome-mediated pyroptosis by regulating DDX3X - PubMed
4 hours ago
- #NLRP3 inflammasome
- #African swine fever
- #Pyroptosis
- African swine fever virus (ASFV) infection causes severe hemorrhagic disease in pigs, leading to excessive inflammatory responses and tissue damage.
- ASFV utilizes the NLRP3 inflammasome to induce pyroptosis and inflammatory responses, compensating for the non-functional porcine AIM2 pseudogene.
- EP364R, identified from over 150 ASFV-encoded proteins, drives NLRP3-mediated pyroptosis and high-level cytokine production.
- EP364R expression in mice increases pro-inflammatory cytokines and causes splenomegaly, while NLRP3-knockout mice show no pyroptosis effects.
- DDX3X helicase acts as a molecular bridge, enabling EP364R to interact with NLRP3, promoting inflammasome aggregation and activation.
- EP364R binds to all domains of DDX3X, while DDX3X interacts with the NACHT and LRR domains of NLRP3.
- HAMNO, identified from a natural compound library, inhibits EP364R by binding to specific residues (E256, K259, D260), suppressing ASFV replication.
- The study provides insights into ASFV-induced pyroptosis and cytokine release, aiding in vaccine and therapy development for African swine fever.