title: Roles of p53 in herpes simplex virus 1 replication.
abstract: p53 is a critical factor in the cellular response to a broad range of stress factors through its ability to regulate various cellular pathways. In this study, tandem affinity purification of transiently expressed herpes simplex virus 1 (HSV-1) regulatory protein ICP22 coupled with mass spectrometry-based proteomics technology and subsequent analyses showed that ICP22 interacted with p53 in HSV-1-infected cells. In p53(-/-) cells, replication of wild-type HSV-1 was reduced compared to that in parental p53(+/+) cells, indicating that p53 had a positive effect on HSV-1 replication. In contrast, the levels of viral replication of an ICP22-null mutant virus were similar in both p53(-/-) and p53(+/+) cells. At 2 h postinfection, the level of expression of ICP27, an essential viral regulatory protein, in p53(-/-) cells infected with wild-type HSV-1 or the ICP22-null mutant virus was lower than in p53(+/+) cells. In contrast, at 18 h postinfection, the level of expression of ICP0, a critical viral regulatory protein, in p53(-/-) cells infected with the ICP22-null mutant virus was higher than in p53(+/+) cells, although the levels of ICP0 expression in p53(-/-) and p53(+/+) cells infected with wild-type HSV-1 were almost identical. These results suggested that p53 overall promoted HSV-1 replication and that p53 played both positive and negative roles in HSV-1 replication: upregulating ICP27 expression very early in infection and downregulating ICP0 expression later in infection, which was antagonized by ICP22.
authors.affiliation: Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Maruzuru
authors.forename: Hikaru
authors.initials: H
authors.lastname: Fujii
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oyama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kozuka-Hata
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
mesh_terms: D000818:Animals; D002460:Cell Line; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C057294:ICP22 protein, human herpesvirus 1; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1