1. ¹Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, Canada
2. ²Department of Microbiology & Immunology, McGill University, Montreal, Canada
3. ³Department of Medicine and Oncology, McGill University, Montreal, Canada

Correspondence: Dr J Hiscott, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Ste. Catherine, Montreal, Quebec, Canada H3T1E2. E-mail: john.hiscott@mcgill.ca

Abstract

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 IB kinase (IKK) complex and related kinases TBK-1 and IKK. Activation of the nuclear factor B (NF-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-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-B in the host innate immune response and the multitude of strategies used by different viruses to short circuit the NF-B pathway.