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Infected cell protein 0 (ICP0) is a multifunctional immediate-early protein encoded by the RL2 gene of Herpes Simplex Virus type 1 (HSV-1) (UniProt P08393). It serves as a master regulator of the viral life cycle, functioning primarily as a RING-type E3 ubiquitin ligase that targets host antiviral factors for proteasomal degradation (PubMed 30996104). By dismantling nuclear domain 10 (ND10) structures and degrading proteins such as PML, Sp100, and IFI16, ICP0 effectively neutralizes the host's intrinsic and innate immune defenses (PubMed 21453306). This activity is crucial for the efficient initiation of lytic infection and the successful reactivation of the virus from latency in sensory neurons (PubMed 11152501). Beyond its ligase activity, ICP0 also acts as a promiscuous transactivator that enhances the expression of all classes of viral genes (PubMed 11447293). Given its essential role in overcoming cellular repression and promoting viral spread, ICP0 is a high-priority target for the development of next-generation antivirals, particularly for treating resistant HSV-1 strains (PubMed 30996104).
Inhibition of E3 ubiquitin ligase activity to prevent degradation of host antiviral proteins and block viral reactivation.
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