Differential Regulation of NF-κB Signaling during Human Cytomegalovirus Infection

NF-κB transcription factors are key regulators of immune and stress responses, apoptosis, and differentiation.Human cytomegalovirus (HCMV) activates or represses NF-κB signaling at different times during infection.An initial increase in NF-κB activity occurs within a few hours of infection.The virus appears to adapt to this change since initial viral gene expression is promoted by the elevated NF-κB activity.Because NF-κB upregulates innate immune responses and inflammation, it has also been suggested that HCMV needs to downregulate NF-κB signaling.Recent studies have shown that HCMV has various mechanisms that inhibit NF-κB signaling.HCMV reduces cell surface expression of tumor necrosis factor receptor 1 (TNFR1) and blocks the DNA binding activity of NF-κB.Furthermore, some HCMV tegument proteins antagonize NF-κB activation by targeting the key components of NF-κB signaling at late stages of infection.In this review, we summarize the recent findings on the relationship between HCMV and NF-κB signaling, focusing, in particular, on the viral mechanisms by which the NF-κB signaling pathway is inhibited.