Human cytomegalovirus (HCMV) has evolved sophisticated ways to bypass cellular defences and replicate its genome inside the host nucleus. In this project, we study the “tug of war” between host PML nuclear bodies, which recognise and silence viral DNA, and viral UL112-113 proteins, which assemble into dynamic condensates and later into fibers that shield and replicate the genome. To unravel these opposing processes, we combine advanced live-cell imaging, biochemical assays, structural predictions, and high-resolution cryo-electron microscopy (cryo-EM). Cryo-EM allows us to visualise how UL112-113 proteins undergo liquid-to-fiber transitions and how small molecules can block this assembly, offering potential new antiviral strategies. Together with RNA interactome profiling and single-cell microscopy, this integrative approach provides a detailed picture of how nuclear architecture is remodelled during HCMV infection and highlights novel therapeutic entry points.