Transmitted by the bite of mosquitoes, dengue virus (DENV) is the most important arboviral pathogen in humans. Currently no drug therapy or vaccine is available for dengue fever, leaving vector control as the major way to protect human populations. The endosymbiotic bacterium Wolbachia has been proposed as a potential agent for vector control, because it can not only spread within mosquito populations via manipulation of mosquito reproduction but also inhibit transmission of DENV in mosquitoes. In order to develop Wolbachia-based control strategies to prevent DENV infection, we have to better understand the interactions between DENV and Wolbachia in mosquitoes. Aedes albopictus naturally carries Wolbachia infection, however, Wolbachia-mediated viral resistance was not observed in Ae. albopictus. In this study, we demonstrated that the native Wolbachia induce a resistance to DENV in Wolbachia density-dependent manner in Ae. albopictus. A decrease in Wolbachia density within the host cells results in increased dengue infection. We provide evidence that a very low Wolbachia density in mosquito tissues where DENV resides and travels could contribute to the absence of Wolbachia-mediated resistance to DENV in Ae. albopictus. We also investigated the impact of Wolbachia infection on DENV life cycle. We report here that Wolbachia is able to inhibit the intracellular accumulation of DENV in Aedes. aegypti mosquito cells. We showed that Wolbachia infection inhibits DENV binding to mosquito Aag2 cells. We then compared the DENV negative strand RNA levels in Wolbachia infected and uninfected mosquito cells. Wolbachia infection also inhibits DENV replication in mosquito Aag2 cells.To further investigate Wolbachia-DENV interactions in mosquito, we carried out microarray and real-time PCR analyses to define host cell transcriptional responses that are induced by Wolbachia infection. Our data indicates that sixteen previously identified DENV host factors were up-regulated in mosquito cells infected with Wolbachia. An RNA interference (RNAi) screen revealed eleven host factors that are associated with Wolbachia-mediated viral resistance. Our data provides several potential targets for interrupting dengue virus infection in mosquitoes.
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