Innate immune antiviral defenses are essential for controlling viral infection. These responses include production of type I IFN and pro-inflammatory cytokines, expression of antiviral effector genes, and activation of the adaptive immune response. Much of these responses are initiated when a host cell detects and response to an invading viral pathogen through specific pattern recognition receptors. Our laboratory focuses on understanding how the RIG-I like receptors detect, respond, and regulate immunity to viral infection. The RIG-I-like receptors, which include RIG-I, MDA5, and LGP2, are expressed basally in nearly all cell types in the boday and are induced to increased levels during viral infection and in response to type I IFNs. Using West Nile virus, and emerging RNA virus that is the leading cause of mosquito-borne encephalitis in humans within the United States, we have been dissecting the host immune response to infection. Through these studies, we have identified that the RIG-1 like receptors are essential for protection, triggering type I IFN-mediated responses and regulating innate immune, humoral and cell-mediated responses. Current areas of research include defining virus-host interactions that regulate immunity to Flavivirus infection, understanding how the RIG-I like receptors regulate B and T cell immunity, and how the RIG-I like receptors can be targeted to serve as potential vaccine adjuvants.