Prolonged activation of NF-κB by human cytomegalovirus promotes efficient viral replication and late gene expression

Infection of fibroblasts by human cytomegalovirus (HCMV) rapidly activates the NF-κB signaling pathway, which we documented promotes efficient transactivation of the major immediate-early promoter (DeMeritt, I.B., Milford, L.E., Yurochko, A.D. (2004). Activation of the NF-κB pathway in human cytomegalovirus-infected cells is necessary for efficient transactivation of the major immediate-early promoter. J. Virol. 78, 4498–4507). Because a second, sustained increase in NF-κB activity following the initial phase of NF-κB activation was also observed, we investigated the role that this prolonged NF-κB activation played in viral replication and late gene expression. We first investigated HCMV replication in cells in which NF-κB activation was blocked by pretreatment with NF-κB inhibitors: HCMV replication was significantly decreased in these cultures. A decrease in replication was also observed when NF-κB was inhibited up to 48 h post-infection, suggesting a previously unidentified role for NF-κB in the regulation of the later class of viral genes.