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-kappa B 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-kappa B 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-kappa B activity following the initial phase of NF-kappa B activation was also observed, we investigated the role that this prolonged NF-kappa B activation played in viral replication and late gene expression. We first investigated HCMV replication in cells in which NF-kappa B activation was blocked by pretreatment with NF-kappa B inhibitors: HCMV replication was significantly decreased in these Cultures. A decrease in replication was also observed when NF-kappa B was inhibited LIP to 48 h post-infection, suggesting a previously Unidentified role for NF-kappa B in the regulation of the later class of viral genes. (c) 2005 Elsevier Inc. All rights reserved.