Manipulation of the nuclear factor-κB pathway and the innate immune response by viruses

Viral and microbial constituents contain specific motifs or pathogen-associated molecular patterns (PAMPs) that are recognized by cell surface-and endosome-associated Toll-like receptors (TLRs). In addition, intracellular viral double-stranded RNA is detected by two recently characterized DExD/H box RNA helicases, RIG-I and Mda-5. Both TLR-dependent and -independent pathways engage the I kappa B kinase (IKK) complex and related kinases TBK-1 and IKK epsilon. Activation of the nuclear factor kappa B (NF-kappa B) and interferon regulatory factor (IRF) transcription factor pathways are essential immediate early steps of immune activation; as a result, both pathways represent prime candidates for viral interference. Many viruses have developed strategies to manipulate NF-kappa B signaling through the use of multifunctional viral proteins that target the host innate immune response pathways. This review discusses three rapidly evolving areas of research on viral pathogenesis: the recognition and signaling in response to virus infection through TLR-dependent and -independent mechanisms, the involvement of NF-kappa B in the host innate immune response and the multitude of strategies used by different viruses to short circuit the NF-kappa B pathway.