Several microorganisms and viruses encode proteins that can inhibit NF-κB activation. Many viruses have developed a number of mechanisms to inhibit NF-κB signaling [153], and three viruses—African swine fever virus (ASFV) [154], rabbit myxoma virus [155], and insect Microplitis demolitor bracovirus [156]—encode IκB-like NF-κB inhibitors. The ASFV encodes the A238L IκB-like protein, which can stably interact with RelA to inhibit TNFα-, IFN-γ-, and phorbol ester-induced NF-κB-DNA binding [157]. The poliovirus 3C protease cleaves RelA to reduce NF-κB signaling [158]. In addition, several viruses have adaptor-like or small proteins that inhibit IKK activity [153]. For example, the MC160 protein of Molluscum contagiosum [159] and the nonstructural 5B protein of the hepatitis C virus [160] appear to be IKKα-specific and thus may specifically inhibit the noncanonical NF-κB pathway.
