John Hiscott, Hakju Kwon, Pierre Génin
Modulation of the NF-κB pathway by viruses. Mechanisms of activation of the NF-κB pathway by HTLV-1–Tax protein include direct association of Tax and IKK-γ or latent NF-κB/IκBα complexes. EBV LMP1–mediated signaling results in the recruitment of TRADD, which interacts with TRAF2 and RIP kinase to activate NF-κB. TRAF2 potentially activates NIK and MEKK1, which phosphorylate and activate the IKK complex. Other mechanisms of activation of the NF-κB pathway by viruses include direct activation of MEKK1 and PKC by HBx protein from HBV, persistent degradation of IκBα by SV, ER overload by influenza and adenovirus, and generation of reactive oxygen intermediates by influenza virus. NF-κB activation is inhibited at either the IKK activation step by E1A of adenovirus or at the IκBα degradation step by MV and HCV core C protein. Lines in green with a + indicate activation of NF-κB, while lines in red with a – indicate inhibition of NF-κB.