Herpesvirus-mediated stabilization of ICP0 expression neutralizes restriction by TRIM23
Xing Liu, Dhiraj Acharya, Eric Krawczyk, Chase Kangas, Michaela U. Gack, Bin He
Abstract
Significance Herpes simplex viruses (HSV) can switch between lytic and latent infections, which are lifelong sources of recurrent diseases. In this process, the immediate early protein ICP0 crucially drives herpesvirus gene expression or reactivation from latency. The regulatory network of ICP0 expression is, however, largely obscure. We uncover that the HSV-1 virulence factor γ 1 34.5 interacts with and stabilizes ICP0. We also demonstrate that TRIM23, a cellular E3 ligase, triggers proteasomal degradation of ICP0 in the absence of γ 1 34.5. As such, removal of γ 1 34.5 or ICP0 from HSV-1 cripples viral growth, whereas ablation of TRIM23 restores viral production. These findings provide a framework of virus–host regulatory circuits, which may help in the rational design of antiviral or oncolytic therapeutics.