Disruption of the p53-p21 pathway inhibits efficiency of the lytic-replication cycle of herpes simplex virus type 2 (HSV-2)

► We observed in vitro HSV-2 proliferation increased cellular p21 expression, p53 Ser20 phosphorylation. ► Knockdown of endogenous p21 by specific siRNAs severely impaired HSV2 propagation. ► Cells lacking endogenous p53 mechanism were defective in p21 up-regulation and HSV-2 production. ► We conclude that the p53-p21 pathway is required for efficient lytic replication of HSV-2.