E3 ubiquitin-protein ligase ICP0 (ICP0)

E3 ubiquitin-protein ligase ICP0, also known as Infected Cell Protein 0, is a multifunctional immediate-early protein of the Herpes Simplex Virus 1 (HSV-1) that is essential for viral pathogenesis [1, 6]. It contains a RING-finger domain that functions as an E3 ubiquitin ligase, directing the proteasomal degradation of host antiviral proteins such as PML, Sp100, and IFI16 [1, 15]. By dismantling these intrinsic and innate immune defenses, ICP0 facilitates the onset of lytic infection and the transition of the viral genome into a transcriptionally active state [2, 10]. Crucially, ICP0 is also a key regulator of the switch between latency and reactivation, making it a vital factor for the recurrence of herpes diseases [3, 13]. While current standard-of-care treatments like acyclovir target viral DNA polymerase, they fail to prevent reactivation from latency; thus, ICP0 has emerged as a high-priority target for novel antivirals [7, 10]. Therapeutic strategies under investigation include small-molecule inhibitors of its ligase activity and proteolysis-targeting chimeras (PROTACs) designed to induce its degradation [3, 10].

Other names

Infected cell protein 0Alpha-0 proteinImmediate-early protein IE110RING-type E3 ubiquitin transferase ICP0VMW110Trans-acting transcriptional protein ICP0RL2

Inhibition of E3 ubiquitin ligase activity or induction of targeted protein degradation (PROTAC)