Depletion of Intracellular Zinc Inhibits the Ubiquitin Ligase Activity of Viral Regulatory Protein ICP0 and Restricts Herpes Simplex Virus 1 Replication in Cell Culture

The viral ubiquitin ligase ICP0 stimulates the onset of HSV-1 lytic infection and productive reactivation of viral genomes from latency. In order to mediate these processes, it requires its C3HC4 RING finger domain, a tertiary structural fold that is coordinated by the binding of two zinc (Zn2+) atoms. Here we formally demonstrate that Zn2+ binding and intracellular Zn2+ levels are critical for ICP0's biochemical activity and that depletion of intracellular Zn2+ severely attenuates HSV-1 replication.