YIPF5 orchestrates the maturation of PRRSV replication organelles by bridging the C-shaped intermediate to spherical DMV transition
Description
The biogenesis of double-membrane vesicles (DMVs) is a fundamental yet poorly understood process in the replication of nidoviruses. Here, we identify the host factor YIPF5 as a critical spatiotemporal organizer that orchestrates the maturation of PRRSV replication organelles. By integrating functional assays with advanced microscopy, we demonstrate that PRRSV hijacks YIPF5 to anchor nsp2/3 complexes at the perinuclear region. Mechanistically, we define a two-stage assembly model: nsp2-nsp3 complexes initiate membrane curvature to form zippered intermediates, while YIPF5 acts as an essential scaffold to drive the structural transition from C-shaped intermediates to mature, spherical DMVs. Our findings delineate a conserved regulatory checkpoint in nidovirus replication and position the YIPF5-nsp3 axis as a potential target for broad-spectrum antiviral strategies.