We propose that IPS-1 coordinates an innate/adaptive immune interface wherein IPS-1-signaling after RLR engagement regulates the quantity, quality, and balance of the subsequent immune response. The integrity of the innate/adaptive immune interface is central to the eliminating virus but also restricting immunopathogenesis and inflammation during infection. RLR signaling is essential for triggering the innate immune response to RNA viruses that cause human disease, including the influenza viruses, respiratory syncytial virus and other paramyxoviruses, picornaviruses, reoviruses, flaviviruses, and hepatitis C virus [14, 19, 22] . Thus, in addition to WNV, IPS-1-dependent RLR signaling will likely have a broad impact for the control of inflammation, immune response quality, and viral disease.