Target intelligence / Profile preview

Infected cell polypeptide 4 (ICP4)

Target
ICP4
Molecular classification
Transcription factor (virus-encoded), DNA-binding protein, Nucleoprotein
01

Overview

ICP4 is a large, multi-domain viral protein (~175 kDa) encoded by the herpes simplex virus alpha 4 gene. It is synthesized early after infection and persists throughout all infection phases[1][4][10]. ICP4 possesses both DNA-binding and transcriptional activation domains, interacting specifically with viral DNA at promoter regions to facilitate the recruitment and stabilization of cellular transcription machinery—including TFIID, TBP, and Mediator—enabling the robust transcription of viral early and late genes[1][2][3][5][7][8][9][10]. ICP4 is essential for viral replication: in its absence, viral DNA replication and late gene synthesis fail, and no infectious virus is produced[1][3][6]. Post-translational modifications (adenylation and guanylation) have been observed in ICP4, and the protein shares some domains with cellular GTP-binding proteins[4]. ICP4 is a validated antiviral target for gene silencing approaches such as siRNA, underpinning its biological and therapeutic relevance[6].

Other names
ICP4Infected cell protein 4Alpha 4 protein
02

Mechanism of action

Transcriptional inhibition through RNA interference (siRNA)[6] Suppression of ICP4-mediated gene activation reduces viral replication and transcription of viral genes[6]

03

Biological functions

Activation of viral gene transcription[1][3][4][10]Recruitment of RNA polymerase II and cellular general transcription factors (TFIID, TBP, Mediator)[1][2][5][7][8]Promotion of transcription preinitiation complex formation[3][5][7][9]Circularization of viral genome and formation of replication compartments[6]Regulation of immediate-early, early, and late gene expression during HSV infection[3][6][10]
04

Disease associations

Infection (essential for HSV-1 and HSV-2 replication)[1][3][4][6][10]
05

Safety considerations

Virally encoded, thus target specificity needed for host safetyRisk of off-target immune responses for gene therapy approaches[6]
06

Interacting drugs

Small interfering RNAs (siRNAs) targeting ICP4 mRNA[6]

1 more in the full profile.

07

Biomarkers

ICP4 expression (marker for HSV infection and lytic cycle)Decrease in early and late HSV gene products upon ICP4 inhibition[1][3][6]

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