Analysis of Aedes aegypti microRNAs in response to Wolbachia wAlbB infection and their potential role in mosquito longevity

Abstract

The mosquito Aedes aegypti is the primary vector of a range of medically important viruses including dengue, Zika, West Nile, yellow fever, and chikungunya viruses. The endosymbiotic bacterium Wolbachia pipientis wAlbB strain has emerged as a promising biocontrol agent for blocking viral transmission by Ae. aegypti. In order to predict and manage the long-term efficacy of its application in the field, a thorough understanding of the molecular interactions between symbiont, host, and pathogen is required. Wolbachia are known to influence host physiology in a variety of ways including reproduction, innate immunity, metabolism, and longevity. MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that are important regulators of gene expression in eukaryotes and viruses. A number of miRNAs have been functionally described in Drosophila and mosquitoes as having roles in regulating a broad range of biological processes, as well as facilitating Wolbachia maintenance. We generated the first chromosomal map of Ae. aegypti miRNAs, and compared the miRNA expression profiles between a wAlbB-transinfected Ae. aegypti mosquito line and a tetracycline cleared derivative using deep small RNA-sequencing. We found a number of miRNAs to be modulated by wAlbB infection. We also found that some miRNAs were upregulated with age in a manner that was affected by wAlbB. By selectively inhibiting some differentially expressed miRNAs, we identified miR-2946-3p and miR-317-3p as effecting mosquito longevity.ImportanceWolbachia is an endosymbiotic bacterium found in about 65% of insect species. It is mostly known for reproductive manipulations of the host, and also blocking replication of negative sense RNA viruses. Transinfection of Wolbachia into Aedes aegypti mosquitoes, which transmit a variety of arboviruses, including dengue virus, has provided a novel biological approach in reducing transmission of arboviruses. To gain a better understanding of Wolbachia-mosquito interactions, we investigated the impact of Wolbachia on the microRNA profile of Ae. aegypti mosquitoes. Besides identifying several differentially expressed microRNAs and their putative target genes, we found alterations of microRNAs in mosquitoes due to age. Inhibition of two miRNAs led to reduced mosquito life span. The outcomes provide insights into underlying molecular mechanisms involved in Wolbachia-host interactions.