Regulation of the transcription and replication cycle of human cytomegalovirus is insensitive to genetic elimination of the cognate NF-κB binding sites in the enhancer

The role of NF-kappa B in regulating human cytomegalovirus (HCMV) replication and gene transcription remains controversial. Multiple, functional NF-kappa B response elements exist in the major immediate-early promoter (MIEP) enhancer of HCMV, suggesting a possible requirement for this transcription factor in lytic viral replication. Here we demonstrate by generating and analyzing HCMVs with alterations in the MIEP-enhancer that, although this region is essential for HCMV growth, none of the four NF-kappa B response elements contained within the enhancer are required for MIE gene expression or HCMW replication in multiple cell types. These data reveal the robustness of the regulatory network controlling the MIEP enhancer.