title: Overexpression of the ubiquitin-specific protease 7 resulting from transfection or mutations in the ICP0 binding site accelerates rather than depresses herpes simplex virus 1 gene expression.
abstract: Earlier studies reported that ICP0, a key regulatory protein encoded by herpes simplex virus 1 (HSV-1), binds ubiquitin-specific protease 7 (USP7). The fundamental conclusion of these studies is that depletion of USP7 destabilized ICP0, that ICP0 mediated the degradation of USP7, and that amino acid substitutions in ICP0 that abolished binding to USP7 significantly impaired the ability of HSV-1 to replicate. We show here that, indeed, depletion of USP7 leads to reduction of ICP0 and that USP7 is degraded in an ICP0-dependent manner. However, overexpression of USP7 or substitution in ICP0 of a single amino acid to abolish binding to USP7 accelerated the accumulation of viral mRNAs and proteins at early times after infection and had no deleterious effect on virus yields. A clue as to why USP7 is degraded emerged from the observation that, notwithstanding the accelerated expression of viral genes, the plaques formed by the mutant virus were very small, implying a defect in virus transmission from cell to cell.
authors.affiliation: Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, Illinois, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Kalamvoki
authors.forename: Haidong
authors.initials: H
authors.lastname: Gu
authors.forename: Bernard
authors.initials: B
authors.lastname: Roizman
mesh_terms: D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D057809:HEK293 Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D000076084:Ubiquitin-Specific Peptidase 7; D014709:Vero Cells
chemical_list: D017931:DNA Primers; D017874:Immediate-Early Proteins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7