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

Jui Cheng Hsieh; Ryan Kuta; Courtney R. Armour; Paul E. Boehmer

doi:10.1016/j.virol.2014.04.019

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

Jui Cheng Hsieh, Ryan Kuta, Courtney R. Armour, Paul E. Boehmer

Basic Medical Sciences, Phoenix

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English (US)
Pages (from-to)	45-54
Number of pages	10
Journal	Virology
Volume	460-461
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2014.04.019
State	Published - Jul 2014

Keywords

Gene expression
Herpes simplex virus 1
P53
Responsive elements

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2014.04.019

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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.",

keywords = "Gene expression, Herpes simplex virus 1, P53, Responsive elements",

author = "Hsieh, {Jui Cheng} and Ryan Kuta and Armour, {Courtney R.} and Boehmer, {Paul E.}",

note = "Funding Information: This work was supported by Grant GM62643 from the National Institutes of Health, United States .",

year = "2014",

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doi = "10.1016/j.virol.2014.04.019",

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AU - Hsieh, Jui Cheng

AU - Kuta, Ryan

AU - Armour, Courtney R.

AU - Boehmer, Paul E.

N1 - Funding Information: This work was supported by Grant GM62643 from the National Institutes of Health, United States .

PY - 2014/7

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N2 - 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.

AB - 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.

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KW - Responsive elements

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

Abstract

Keywords

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