Requirement for uracil-DNA glycosylase during the transition to late-phasecytomegalovirus DNA replication

Cytomegalovirus gene UL114, a homolog of mammalian uracil-DNA glycosylase ( UNG), is required for efficient viral DNA replication. In quiescent fibrobl asts, UNG mutant virus replication is delayed for 48 h and follows the viru s-induced expression of cellular UNG. In contrast, mutant virus replication proceeds without delay in actively growing fibroblasts that express host c ell UNG. In the absence of viral or host cell UNG expression, mutant virus fails to proceed to late-phase DNA replication, characterized by rapid DNA amplification. The data suggest that uracil incorporated early during wild- type viral DNA replication must be removed by virus or host UNG prior to la te-phase amplification and encapsidation into progeny virions. The process of uracil incorporation and excision may introduce strand breaks to facilit ate the transition from early-phase replication to late-phase amplification .