NF-κB is a pivotal transcription factor that controls cell survival and 
proliferation in diverse physiological processes. The activity of NF-κB is 
tightly controlled through its cytoplasmic sequestration by specific inhibitors, 
IκBs. Various cellular stimuli induce the activation of an IκB kinase, which 
phosphorylates IκBs and triggers their proteasomal degradation, causing nuclear 
translocation of activated NF-κB. Under normal conditions, the activation of 
NF-κB occurs transiently, thus ensuring rapid but temporary induction of target 
genes. Deregulated NF-κB activation contributes to the development of various 
diseases, including cancers and immunological disorders. Accumulated studies 
demonstrate that the NF-κB signaling pathway is a target of several human 
oncogenic viruses, including the human T cell leukemia virus type 1, the Kaposi 
sarcoma-associated herpesvirus, and the Epstein-Bar virus. These viruses encode 
specific oncoproteins that target different signaling components of the NF-κB 
pathway, leading to persistent activation of NF-κB. This chapter will discuss 
the molecular mechanisms by which NF-κB is activated by the viral oncoproteins.