Herpes simplex virus infected cell protein 27 (ICP27)

Herpes simplex virus infected cell protein 27 (ICP27) is an immediate-early regulatory protein encoded by HSV-1. ICP27 is indispensable for efficient viral replication and reactivation from latency in neurons. It orchestrates viral gene expression post-transcriptionally by interacting with viral and host proteins, including cellular RNA polymerase II, mRNA processing factors, and nuclear export adaptors. ICP27 inhibits host RNA splicing and promotes export of intronless viral RNA, blocks host transcription termination by binding CPSF, and enhances translation of viral mRNAs. It also suppresses host innate immunity by antagonizing the cGAS-STING pathway, limiting type I interferon induction in macrophages. Structurally, ICP27 contains a conserved dimerization domain (IHD), an N-terminal disordered region with an RGG-box for RNA binding, and a nuclear transport signal essential for its dynamic intracellular trafficking. ICP27 homologs are found across the Herpesviridae, but only HSV-1 ICP27 is studied as a candidate therapeutic target. ICP27’s critical functions make it a key molecule for antiviral research, but as of August 2025, no drugs in clinical use directly target this protein.

Other names

ICP27Infected cell protein 27HSV-1 ICP27Herpes simplex virus type 1 regulatory protein ICP27

Drugs/inhibitors could theoretically block the RNA-binding activity (by interfering with the RGG-box), disrupt dimerization (via the IHD domain), or inhibit known protein-protein interactions critical for mRNA export or host transcription modulation.