Differential Regulation of NF-kappaB Signaling during Human Cytomegalovirus Infection

ABSTRACT

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