Cytomegalovirus immediate-early 1 protein (IE1 (also IE72 for the 72-kDa HCMV isoform))

IE1 is an abundant immediate-early HCMV protein (~72 kDa) that localizes to the nucleus, colocalizes with and binds PML via a conserved globular core domain, and disrupts or functionally neutralizes PML nuclear bodies to overcome intrinsic antiviral restriction[1][5][7]. Structurally, the IE1 core exhibits a unique all–alpha-helical fold, forming dimers with a conserved interface across species; this fold enables high-affinity binding to the PML coiled-coil domain and induction of PML de-SUMOylation, releasing associated factors (hDaxx, Sp100, ATRX)[1][2][5]. Functionally, IE1 promotes viral transcription by antagonizing histone deacetylation, interacting with HDAC3, and facilitating histone H4 acetylation at viral promoters; HDAC inhibitors can rescue replication defects of IE1-deficient virus, underscoring IE1’s role in chromatin modulation[7]. The C-terminal acidic region contains a STAT-binding motif that compromises STAT-mediated interferon signaling, further aiding immune evasion; the extreme C-terminus includes a chromatin-tethering domain[1]. Species specificity: IE1–PML interactions are adapted to the host species, forming a barrier to cross-species CMV infection; expression of HCMV IE1 can permit rat CMV replication in human cells in experimental systems[5][3]. Multiple crystal structures define the core domain from human, rhesus, and rat CMVs, highlighting a conserved tertiary and quaternary architecture with some flexibility and dimerization features relevant to function[1][2][4][8].

Other names

Immediate-early 1 protein (IE1)IE72 (72-kDa immediate-early 1)Major immediate-early 1 protein of HCMV

For prospective targeting: inhibition of IE1–PML interaction to preserve PML-NB antiviral function. For chromatin-directed approaches: modulation of HDAC activity/IE1–HDAC3 interaction to counter IE1-driven deacetylation antagonism.