Aedes Anphevirus: an Insect-Specific Virus Distributed Worldwide in Aedes Aegypti Mosquitoes That Has Complex Interplays with Wolbachia and Dengue Virus Infection in Cells

Insect-specific viruses (ISVs) of the yellow fever mosquito have been demonstrated to modulate transmission of arboviruses such as dengue virus (DENV) and West Nile virus by the mosquito. The diversity and composition of the virome of , however, remains poorly understood. In this study, we characterized Aedes anphevirus (AeAV), a negative-sense RNA virus from the order AeAV identified from cell lines was infectious to both and cells but not to three mammalian cell lines. To understand the incidence and genetic diversity of AeAV, we assembled 17 coding-complete and two partial genomes of AeAV from available transcriptome sequencing (RNA-Seq) data. AeAV appears to transmit vertically and be present in laboratory colonies, wild-caught mosquitoes, and cell lines worldwide. Phylogenetic analysis of AeAV strains indicates that as the mosquito has expanded into the Americas and Asia-Pacific, AeAV has evolved into monophyletic African, American, and Asia-Pacific lineages. The endosymbiotic bacterium restricts positive-sense RNA viruses in Reanalysis of a small RNA library of cells coinfected with AeAV and produces an abundant RNA interference (RNAi) response consistent with persistent virus replication. We found enhances replication of AeAV compared to a tetracycline-cleared cell line, and AeAV modestly reduces DENV replication The results from our study improve understanding of the diversity and evolution of the virome of and adds to previous evidence that shows does not restrict a range of negative-strand RNA viruses. The mosquito transmits a number of arthropod-borne viruses (arboviruses), such as dengue virus and Zika virus. Mosquitoes also harbor insect-specific viruses that may affect replication of pathogenic arboviruses in their body. Currently, however, there are only a few insect-specific viruses described from in the literature. Here, we characterize a novel negative-strand virus, AeAV. Meta-analysis of samples showed that it is present in mosquitoes worldwide and is vertically transmitted. -transinfected mosquitoes are currently being used in biocontrol, as they effectively block transmission of several positive-sense RNA viruses in mosquitoes. Our results demonstrate that enhances the replication of AeAV and modestly reduces dengue virus replication in a cell line model. This study expands our understanding of the virome in as well as providing insight into the complexity of the virus restriction phenotype.