Herpes simplex virus 2 infected cell protein 4 (ICP4)

Herpes simplex virus 2 (HSV-2) infected cell protein 4 (ICP4) is a critical immediate-early regulatory protein essential for the viral lytic cycle (UniProt P04488). It functions as a multifunctional transcription factor that coordinates the temporal expression of viral genes by activating early and late genes while autorepressing its own expression (Smith et al., 2021, Journal of Virology). ICP4 exerts its effects by binding to specific DNA sequences and interacting with host cell basal transcription factors, such as TATA-binding protein (TBP) and TFIIB, to recruit RNA polymerase II to viral promoters (PubMed: 28254978). Because the virus cannot replicate or produce progeny without functional ICP4, it is considered a high-priority therapeutic target for anti-herpetic interventions. Current research focuses on novel strategies to inhibit ICP4, including CRISPR/Cas9 gene editing (e.g., BD111) and antisense oligonucleotides designed to disrupt its synthesis or DNA-binding activity (Nature Biomedical Engineering, 2021). Targeting ICP4 offers a potential advantage over traditional nucleoside analogs by halting the viral replication cycle at an earlier stage and potentially addressing latent infections in the nervous system.

Other names

RS1Immediate-early protein ICP4IE175Transcriptional activator ICP4Protein RS1HSV-2 ICP4

Inhibition of viral immediate-early protein synthesis or function, leading to the suppression of downstream early and late viral gene expression and replication.