| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3424039 | Virology | 2014 | 10 Pages |
•Identification of p53 responsive elements (RE) in the vicinity of the replication origins in HSV‐1.•Binding by p53 to the candidate HSV‐1 RE in vitro and in vivo.•HSV‐1 p53RE confer p53‐depdendent transcriptional activation onto a reporter gene.•p53‐dependent repression of essential viral proteins proximal to the HSV‐1 p53RE.
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.
