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

• 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.