title: Identification of two novel functional p53 responsive elements in the herpes simplex virus-1 genome.
abstract: Analysis of the herpes simplex virus-1 (HSV-1) genome reveals two candidate p53 responsive elements (p53RE), located in proximity to the replication origins oriL and oriS, referred to as p53RE-L and p53RE-S, respectively. The sequences of p53RE-L and p53RE-S conform to the p53 consensus site and are present in HSV-1 strains KOS, 17, and F. p53 binds to both elements in vitro and in virus-infected cells. Both p53RE-L and p53RE-S are capable of conferring p53-dependent transcriptional activation onto a heterologous reporter gene. Importantly, expression of the essential immediate early viral transactivator ICP4 and the essential DNA replication protein ICP8, that are adjacent to p53RE-S and p53RE-L, are repressed in a p53-dependent manner. Taken together, this study identifies two novel functional p53RE in the HSV-1 genome and suggests a complex mechanism of viral gene regulation by p53 which may determine progression of the lytic viral replication cycle or the establishment of latency.
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, 425 North 5th Street, Phoenix, AZ 85004-2157, USA. Electronic address: hsieh@email.arizona.edu.
authors.forename: Jui-Cheng
authors.initials: JC
authors.lastname: Hsieh
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, 425 North 5th Street, Phoenix, AZ 85004-2157, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Kuta
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, 425 North 5th Street, Phoenix, AZ 85004-2157, USA.
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Armour
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, 425 North 5th Street, Phoenix, AZ 85004-2157, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Boehmer
mesh_terms: D001483:Base Sequence; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D006561:Herpes Simplex / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D018741:Replication Origin; D020218:Response Elements; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Gene expression; Herpes simplex virus 1; Responsive elements; p53