Pathogen recognition systems. The innate immune system senses viral pathogens by recognizing distinct pathogen-associated molecular patterns (PAMPs) using various pattern recognition receptors (PRRs). Two of the best-characterized virus-sensing PRRs include member of the Toll-like receptors (TLRs) and retinoic acid inducible gene-I- (RIG-I-) like receptors (RLRs) families. These PRRs couple the recognition of viral PAMPs to the induction of proinflammatory cytokines through various signaling cascades. The cytosolic RNA helicase receptors MDA5 and RIG-I initiate the cascade by recruiting the Cardif/TBK1 complex after sensing viral RNA. This activates the kinase TBK1 to phosphorylate interferon regulatory factor (IRF)-3 and IRF7, resulting in their nuclear translocation and the transcription of IFNα/β. The cell surface receptor TLR4, in partnership with CD14, couples the recognition of respiratory syncytial virus fusion protein [78] to cytokine induction by signaling through the MyD88-dependent as well as the MyD88-independent pathways. The endosomal TLRs, TLR7, TLR8, and TLR9 also signal through MyD88 to activate inflammatory cytokines such as TNF, IL-6, and IFN-α/β. The other endosomal TLR (TLR3) signals through the MyD88-independent pathway via the TIR domain-containing adaptor molecule TRIF. Via TRIF, TLR3 signaling can activate NF-kB using TRAF6, and in addition, can induce type I IFN expression probably via TRAF3, TBK1, and IRF3.