Arthropod-borne (arbo) viruses are transmitted by vectors, such as mosquitoes, among susceptible vertebrates. Arboviruses, such as West Nile virus, are a major public health and veterinary concern, yet the mosquito immune response against these pathogens is poorly understood. Several innate immunity mechanisms such as RNAi, Toll, IMD, Jak/STAT and melanisation have proven to be antiviral. Previously we showed that the secreted Culex orthologue of Vago (CxVago) restricts WNV infection by activating the Jak/STAT pathway in a manner similar to mammalian interferon. Activation of this pathway induces nuclear translocation of STAT and transcription of antiviral genes that restrict virus infection in Culex cells. Here we have identified three of these CxVago induced genes as Dengue virus restriction factors (DVRFs), which have been previously described to have antiviral activity in dengue infected Aedes mosquitoes. However the nature of their antiviral proteins remains largely unknown. We investigated the transcription profile and antiviral roles for these genes after treatment with Vago. We also determined the antiviral effect of these genes after infection of Culex cells with Arboviruses from several families. This study also determined the antiviral mechanisms of these Vago activated genes. Our results suggest that DVRF1 is a transmembrane protein that interferes with virus entry in the same manner as interferon induced transmembrane proteins (IFTM) in vertebrates. DVRF2 and DVRF3 are secreted proteins that interact with the virion lowering its infectivity. Experiments are currently in progress to determine if these proteins limit virus spread within the mosquito, from the midgut to the salivary glands. We believe that, unlike RNAi these proteins restrict viral spread after a primary infection has been established in the midgut. This research will increase our understanding of the virus-vector interaction and factors influencing viral infection of mosquitoes.