Potential Role for p53 in the Permissive Life Cycle of Human Cytomegalovirus

Abstract

Infection of primary fibroblasts with human cytomegalovirus (HCMV) causes a rapid stabilization of the cellular protein p53. p53 is a major effector of the cellular damage response, and activation of this transcription factor can lead either to cell cycle arrest or to apoptosis. Viruses employ many tactics to avoid p53-mediated effects. One method HCMV uses to counteract p53 is sequestration into its viral replication centers. In order to determine whether or not HCMV benefits from this sequestration, we infected a p53 ؊/؊ fibroblast line. We find that although these cells are permissive for viral infection, several parameters are substantially altered compared to wild-type (wt) fibroblasts.

Restriction of human herpesvirus 6B replication by p53

“…Several DNA viruses have been shown to affect the stabilization and transcriptional activity of p53. HCMV seems to require p53 for its replication in a permissive fibroblast cell line, as p53 2/2 cells delay and decrease the accumulation of infectious viral particles (Casavant et al, 2006). This is in contrast to our findings, and may reveal different roles of p53 during productive and non-productive infections.…”

Transient increases in p53-responsible gene expression at early stages of Epstein-Barr virus productive replication

“…Several studies regarding p53 and human cytomegalovirus (HCMV), a member of beta-herpesvirus family, have demonstrated the elevated levels of p53 protein upon viral infection, whereas the cellular downstream targets of p53 are not activated. 33,34 It was reported that cells infected with HCMV in the absence of p53 produced fewer infectious viral particles, and that the loss of p53 caused the delays of viral protein production and its trafficking. 33 The observed delayed formation of replication centers could result in the delay of viral encapsidation.…”

Cytoplasmic Translocation of p53 by Human Cytomegalovirus Infection

“…These results suggest that p53 might be stabilized and not p53 facilitates the transportation of pp65 from nucleus to cytoplasm and enhances the production of viruses (15).…”

“…Our previous studies show HCMV IE1-72 and UL44 also inhibit p53-dependent transcription in different ways (13,14). Besides transcriptional regulation p53 facilitates the transportation of one of HCMV matrix proteins from nucleus to cytoplasm and induces the production of viruses (15). The sequestration of p53 was reported in the cytoplasm of endothelial cells after HCMV infection (16).…”