In vitro, ICP0 is a biochemically active E3 ubiquitin ligase in the presence of E2 ubiquitin conjugating enzymes (E2s) [UBE2D1 (UbcH5a) and UBE2E1 (UbcH6)] [57], but which E2s are used during infection has remained unclear. Here, UBE2S is linked to infection.