UL123
Domain
The N-terminal region is required for nuclear targeting. The C-terminal 16-amino acid is termed the chromosome-tethering domain (CTD) and is required for the association of IE1, host PML and host STAT2 with the mitotic chromosomes. Targets host nucleosomes by directly binding to the acidic pocket of core histones.
Function
Plays an important role in transactivating viral early genes as well as activating its own promoter, probably by altering the viral chromatin structure (By similarity). Expression of IE1 and IE2 proteins is critical for the establishment of lytic infection and reactivation from viral latency (PubMed:27466417). Disrupts PML-associated ND10 nuclear bodies by interfering with host PML and SP100 sumoylation thereby altering the regulation of type I and type II interferon-induced gene expression (PubMed:27903803, PubMed:34370791). Promotes efficient viral growth by interacting with and directing host SP100 to degradation, leading to enhanced acetylation level of histones (By similarity). In addition, functions in counteracting the host innate antiviral response. Inhibits the type I interferon pathway by directly interacting with and sequestrating host STAT2 (By similarity). Also targets type II interferon pathway by repressing IL6- and STAT3 target genes (By similarity). Repression of STAT3 genes is due to STAT3 nuclear accumulation and disruption of IL6-induced STAT3 phosphorylation by IE1 (PubMed:23903834). This repression is followed by phosphorylation and activation of STAT1 (By similarity). Inhibits host ISG transcription by sequestering host ISGF3 in a PML- and STAT2- binding dependent manner (By similarity). Alters host cell cycle progression, probably through its interaction with host E2F1 or RB1 that overcomes the RB1-mediated repression of E2F-responsive promoters (By similarity).
Post-translational modifications
Sumoylated by host PML (PubMed:28250117). Sumoylation abolishes the interaction with host STAT2 and thus the IE1-mediated repression of interferon-stimulated genes (By similarity).
Sequence Similarities
Belongs to the HHV-5 IE1 protein family.
Cellular localization
- Host nucleus
- Colocalizes with host PML-associated nuclear bodies very early post infection.
Alternative names
Immediate early protein IE1, IE1, 55 kDa immediate-early protein 1, IE1p72, IE72, UL123