Human cytomegalovirus immediate-early protein 1 (IE1) (IE1 (also IE1-72, IE72))

Human cytomegalovirus immediate-early protein 1 (IE1) is a 72‑kDa nuclear phosphoprotein encoded by UL123 and abundantly expressed at the onset of infection; it is a promiscuous transcriptional regulator that activates viral early genes and can autoregulate the major IE promoter, in part by antagonizing histone deacetylation through interaction with HDAC3 to enhance histone acetylation on viral chromatin. IE1 counteracts intrinsic immunity by targeting PML nuclear bodies through a conserved α‑helical core domain that binds PML’s coiled-coil, leading to PML de‑SUMOylation and release of ND10 factors (Daxx, Sp100, ATRX), which supports initiation of lytic replication; the C‑terminal acidic region also binds STAT proteins to dampen interferon signaling. The C‑terminal chromatin‑tethering domain within exon 4–derived sequences (aa 476–491) binds core histones and mitotic chromatin, ensuring efficient viral gene expression across cell division. IE1 is essential for efficient CMV replication at low multiplicity and is a key determinant of viral gene expression and immune evasion, making it a plausible antiviral target, although no approved direct IE1 inhibitors exist.

Other names

IE1IE1-72IE72Major immediate-early protein 1UL123 gene productHCMV IE1Immediate-early 1 protein

For agents targeting pathways modulated by IE1: HDAC inhibition increases histone acetylation to compensate for IE1’s chromatin-activating function, restoring early gene transcription in IE1-null virus