West Nile virus (WNV) and other arthropod-borne viruses are a major public health problem around the world. Although vertebrate immune response to these infections has been well understood, the mechanisms of antiviral immunity in mosquitoes are poorly appreciated. RNAi pathway is considered as one of the major antiviral response to viral infections. Mosquito Dicer-2, responsible for the RNAi-mediated response through the C-terminal RNase-III domain, also contains an N-terminal DExD/H-box helicase domain similar to mammalian RIG-I /MDA5. This domain, in drosophila, was found to be required for activation of an antiviral gene, Vago. Our results show that the Culex ortholog of Vago (CxVago) is upregulated in response to WNV infection in Dicer-2-dependent manner. Further, our data shows that CxVago is a secreted peptide that restricts WNV infection by activation of the Jak-STAT pathway in neighboring cells. Currently these findings are being validated in adult mosquito infection model. Thus, although there is no structural similarity, Vago appears to function as an interferon-like antiviral cytokine in mosquitoes.