Intracellular innate immune defenses and the actions of type I interferon (IFN) provide a first-line of defense against virus infection and are essential for the control of WNV replication, dissemination, and neurovirulence [7] . Innate antiviral immune defenses are triggered through the recognition of conserved pathogen associated molecular pattern (PAMP) motifs within viral products by intracellular pathogen recognition receptor (PRR) proteins in infected cells. PRR signaling directs downstream activation of latent transcription factors, including NF-kB, interferon regulatory factor (IRF)-3 and IRF-7, in a cell type-specific manner to induce antiviral response programs that include expression of proinflammatory cytokines, chemokines, type I IFN, and interferon stimulated genes (ISGs) [7, 8, 9, 10] . The ISG products induced through autocrine and paracrine actions of IFN confer antiviral activity by limiting virus replication and cell-to-cell virus spread. Modulation of IFN signaling has been identified as a virulence feature of pathogenic strains of WNV [11, 12] .