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Abstract
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.
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Table 1.
Summary of the HCMV functions that regulate NF-κB signaling
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