Suppression of the pelo protein by Wolbachia and its effect on dengue virus in Aedes aegypti

The endosymbiont Wolbachia is known to block replication of several important arboviruses, including dengue virus (DENV), in the mosquito vector Aedes aegypti.So far, the exact mechanism of this viral inhibition is not fully understood.A recent study in Drosophila melanogaster has demonstrated an interaction between the pelo gene and Drosophila C virus.In this study, we explored the possible involvement of the pelo protein, that is involved in protein translation, in Wolbachia-mediated antiviral response and mosquito-DENV interaction.We found that pelo is upregulated during DENV replication and its silencing leads to reduced DENV virion production suggesting that it facilities DENV replication.However, in the presence of Wolbachia, specifically in female mosquitoes, the pelo protein is downregulated and its subcellular localization is altered, which could contribute to reduction in DENV replication in Ae. aegypti.In addition, we show that the microRNA aae-miR-2940-5p, whose abundance is highly enriched in Wolbachia-infected mosquitoes, might mediate regulation of pelo.Our data reveals identification of pelo as a host factor that is positively involved in DENV replication, and its suppression in the presence of Wolbachia may contribute to virus blocking exhibited by the endosymbiont. Author summaryDengue infection along with its related disease conditions poses a significant threat to human populations.The pathogen responsible for this infection is dengue virus (DENV), which is primarily transmitted to humans through the bites of Ae. aegypti mosquitoes.Unavailability of vaccines has recently sparked research endeavours aimed at vector control.To date, Wolbachia as an endosymbiotic bacterium, has shown promises as a novel biocontrol agent to restrict DENV replication in mosquitoes through a mechanism that is still elusive.In this study, we investigated the role of pelo in Wolbachia-mosquito-D ENV interactions.We found that the pelo protein is upregulated upon DENV infection facilitating its replication, but Wolbachia infection leads to the suppression of the protein that