Manipulation of the nuclear factor-kappaB 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 IkappaB kinase (IKK) complex and related kinases TBK-1 and IKKvarepsilon. Activation of the nuclear factor kappaB (NF-kappaB) 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-kappaB 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-kappaB in the host innate immune response and the multitude of strategies used by different viruses to short circuit the NF-kappaB pathway.
Hiscott
J
J
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, Canada. john.hiscott@mcgill.ca
Nguyen
T-L A
TL
Arguello
M
M
Nakhaei
P
P
Paz
S
S
D000818:Animals; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007113:Immunity, Innate; D016899:Interferon-beta / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D012328:RNA Viruses / Q000502:physiology*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
D016328:NF-kappa B; D051193:Toll-Like Receptors; D016899:Interferon-beta; D051550:I-kappa B Kinase