HES1 and cytomegalovirus infection: Here we demonstrate that: (1) HCMV infection results in loss of Hes1 protein in NPCs; (2) the HCMV immediate-early 1 protein (IE1) mediates Hes1 protein downregulation through direct interaction, which requires amino acids 451–475; (3) IE1 assembles a Hes1 ubiquitination complex and mediates Hes1 ubiquitination; and (4) IE1 also assembles an Sp100A ubiquitination complex and mediates Sp100A ubiquitination, but does not require amino acids 451–475.