title: Depletion of intracellular zinc inhibits the ubiquitin ligase activity of viral regulatory protein ICP0 and restricts herpes simplex virus 1 replication in cell culture.
abstract: 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 (Zn(2+)) atoms. Here we formally demonstrate that Zn(2+) binding and intracellular Zn(2+) levels are critical for ICP0's biochemical activity and that depletion of intracellular Zn(2+) severely attenuates HSV-1 replication.
authors.affiliation: MRC—University of Glasgow Centre for Virus Research, Glasgow, Scotland, United Kingdom.
authors.forename: Kyle
authors.initials: K
authors.lastname: Grant
authors.forename: Louise
authors.initials: L
authors.lastname: Grant
authors.forename: Lily
authors.initials: L
authors.lastname: Tong
authors.forename: Chris
authors.initials: C
authors.lastname: Boutell
mesh_terms: D002460:Cell Line; D006561:Herpes Simplex / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054829:RING Finger Domains; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D015032:Zinc / Q000378:metabolism*
chemical_list: D017874:Immediate-Early Proteins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D015032:Zinc