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Virology. 2014 Jul;460-461:45-54. doi: 10.1016/j.virol.2014.04.019. Epub 2014 May 29.

Identification of two novel functional p53 responsive elements in the herpes simplex virus-1 genome.

Author information

1
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.
2
Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, 425 North 5th Street, Phoenix, AZ 85004-2157, USA.

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.

KEYWORDS:

Gene expression; Herpes simplex virus 1; Responsive elements; p53

PMID:
25010269
PMCID:
PMC4090806
DOI:
10.1016/j.virol.2014.04.019
[Indexed for MEDLINE]
Free PMC Article

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