Work

Porcine Deltacoronavirus M Protein Binds NLRP3 to Promote Inflammasome Assembly via Competition with TRIM31

Year: 2026

Type: article

Abstract: Porcine deltacoronavirus (PDCoV) infection induces severe intestinal inflammation and acute diarrhea in piglets, resulting substantial economic losses. The NLR family pyrin domain containing 3 (NLRP3) inflammasome, a key component of the innate immune system, drives interleukin (IL)-1β maturation, and its excessive activation is closely linked to viral pathogenesis. However, its role in PDCoV infection remains unclear. Here, we report that PDCoV infection induces IL-1β maturation through NLRP3 inflammasome activation both in vivo and in vitro, and the M protein promotes NLRP3 inflammasome assembly and activation. Mechanistically, M protein directly bound the LRR domain of the NLRP3 protein. Seven residues (M116, H201, T205, K207, R212, Y214, and M217) in the β-sheet core of the M protein formed hydrogen bonds with eight residues (Y861, R920, E949, E1007, Y1009, K1015, N1011, and E1033) in the α-helix groove of the LRR domain, serving as critical determinants of binding. Moreover, the M protein protects NLRP3 from proteasomal degradation by removing tripartite motif-containing 31-mediated K48-linked polyubiquitin chains on NLRP3, thereby stabilizing NLRP3 protein. Collectively, these findings reveal a novel mechanism of NLRP3 inflammasome activation during PDCoV infection, offering valuable insights into PDCoV pathogenesis that may facilitate the design of antiviral agents against PDCoV.

Source: Advanced Science

DOI: 10.1002/advs.76393