Human cytomegalovirus immediate-early 1 protein (IE1) (IE1)

The human cytomegalovirus (HCMV) immediate-early 1 protein (IE1), also known as UL123, is a key viral regulatory protein expressed at the onset of infection to promote lytic replication. IE1 features a conserved globular core domain (IE1CORE) with a unique all-α-helical, femur-shaped tertiary fold that mediates direct binding to the cellular restriction factor promyelocytic leukemia protein (PML), disrupting PML nuclear bodies (PML-NBs) and abrogating their antiviral effects. This core domain, flanked by intrinsically disordered N- and C-terminal regions, also interacts with histone deacetylase 3 (HDAC3) to antagonize histone deacetylation, facilitating de novo acetylation of histones H3 and H4 at viral promoters like the major immediate-early and UL44 loci, thereby enhancing viral gene transcription. Additionally, IE1 binds core histones in a nucleic acid-independent manner, targeting nucleosomes and altering host chromatin structure during infection and mitosis. In HCMV pathogenesis, IE1 ensures progression from immediate-early to early and late phases of replication, particularly critical in immunocompromised individuals where HCMV causes severe disease. Structural adaptations in IE1CORE confer species-specific PML targeting, acting as a barrier to cross-species transmission. No approved drugs directly target IE1, reflecting its role as a viral antagonist rather than a host therapeutic target.

Other names

HCMV IE1UL12372-kDa immediate-early 1 protein