High-dimensional CRISPR-SERS interactomics tracks the topological evolution of plant viral pathogenesis and therapeutic response

-Potato virus Y (PVY) pathosystem, we dissect the longitudinal evolution of infection under ningnanmycin (NNM) treatment. Beyond enabling presymptomatic diagnosis at Day 1, our interactome analysis reveals that chronic infection stabilizes into a regulatory triangle clamped by the Vpg-PUB4 interface, whereas therapeutic relapse manifests as a chaotic, Vpg-centralized network. This work establishes interactome topology as a superior diagnostic metric to viral load, providing a blueprint for identifying drug resistance mechanisms and targeting the specific protein-protein interactions that drive viral persistence.