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