Importantly, under infection conditions that do not saturate or antagonize intrinsic PML-NB host defences (HSV-1 ICP0-null mutant MOI < 1 PFU/cell, Fig 6E; < 25 genome copies/cell, S2 Table), we demonstrate vDNA entry into the nucleus alone is not sufficient to stimulate a robust innate immune response (Figs 6E–6J and 7D). Here, PML is linked to infection.