Tudor-SN promotes early replication of dengue virus in the Aedes aegypti midgut

Abstract

Diseases caused by mosquito-borne viruses have been on the rise for the last decades, despite the implementation of vector control methods primarily based on insecticides. An alternative control method currently in development is the use of lab-engineered mosquitoes that are incapable to carry viruses. This has stimulated efforts to identify optimal target genes that are naturally involved in mosquito antiviral defenses or required for viral replication. Although several antiviral immune pathways such as RNA interference (RNAi) have been previously characterized in mosquitoes, the genes that prevent or promote early viral replication in the midgut remain elusive. Here, we investigated the role of a member of the Tudor protein family, Tudor-SN, upon dengue virus infection in the mosquito Aedes aegypti. Tudor-SN expression was upregulated early after dengue virus infection and was subsequently positively correlated with viral loads in the midgut. Using RNAi-mediated knockdown, we showed that the loss of Tudor-SN reduced dengue virus replication in the Ae. aegypti derived cell line Aag2 and in the midgut of Ae. aegypti females in vivo. Using immunofluorescence assays, we found that Tudor-SN localizes to the nucleolus in both Ae. aegypti and Aedes albopictus cells. Finally, we used a reporter assay to demonstrate that Tudor-SN was not required for RNAi function in vivo. Collectively, these results define a novel proviral role for Tudor-SN upon early dengue virus infection of the Ae. aegypti midgut.