We are interested in emerging and globally important RNA viruses including arthropod-borne viruses as well as respiratory viruses. We use genetic approaches to define host factors that promote infection and understand how these viruses are able to hijack cellular machinery using only a small number of proteins. Furthermore, we are defining mechanisms by which the innate immune system, the first line of defense, can recognize and respond to these invaders. Since much of the recognition is at the level of nucleic acid recognition, and these are RNA viruses, we have been exploring the role of RNA binding proteins and the RNA decay machinery in viral infection and innate antiviral defense against these viruses. We are systematically characterizing innate immune signaling pathways in the diverse cell types targeted by these viruses and exploring strategies to enhance interferon responses to block infection. Our recent findings will be discussed.