Assessing the Potential Interactions between Cellular miRNA and Arboviral Genomic RNA in the Yellow Fever Mosquito, Aedes aegypti.

Pei-Shi Yen,Chun-Hong Chen,Alain Kohl,Anna-Bella Failloux,Vattipally Sreenu

doi:10.3390/v11060540

Abstract

Although the role of exogenous small interfering RNA (siRNA) and P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) pathways in mosquito antiviral immunity is increasingly better understood, there is still little knowledge regarding the role of mosquito cellular microRNA (miRNA). Identifying direct interactions between the mosquito miRNAs and the RNA genome of arboviruses and choosing the relevant miRNA candidates to explore resulting antiviral mechanisms are critical. Here, we carried out genomic analyses to identify Aedes aegypti miRNAs that potentially interact with various lineages and genotypes of chikungunya, dengue, and Zika viruses. By using prediction tools with distinct algorithms, several miRNA binding sites were commonly found within different genotypes/and or lineages of each arbovirus. We further analyzed those miRNAs that could target more than one arbovirus, required a low energy threshold to form miRNA-viralRNA (vRNA) complexes, and predicted potential RNA structures using RNAhybrid software. We predicted miRNA candidates that might participate in regulating arboviral replication in Ae. aegypti. Even without any experimental validation, which should be done as a next step, this study can shed further light on the role of miRNA in mosquito innate immunity and targets for future studies.

Highlights

Emerging and reemerging arthropod-borne viruses are spreading globally in recent decades [1]
93 potential binding sites could be found in chikungunya virus (CHIKV) genome, 151, 130, 123, and 98 potential binding sites found in the genomes of DENV1–4, respectively, and 79 potential binding sites in the Zika virus (ZIKV) genome
CHIKV belongs to the family of Togaviridae and the genus Alphavirus, with three genotypes circulating worldwide: East/Central/South African (ECSA), West African (WA), and Asian

Summary

Introduction

Emerging and reemerging arthropod-borne viruses (arboviruses) are spreading globally in recent decades [1]. The evolution of mosquito-borne RNA viruses and the complex interplay between the vector, the host, and the virus can shape arboviral emergence and re-emergence [3,4]. Infection of the arthropod midgut epithelial cells occurs following ingestion of a viremic blood meal; the ingested virus must disseminate through internal tissues and organs before reaching the salivary glands to be transmitted. The virus has to overcome a series of tissue barriers before being secreted in mosquito saliva when it takes its blood meal [5]. Each barrier has different tissue-specific immune properties, which, once triggered by viral infection, may affect the mosquito’s overall vector competence [6]. Immune responses to arboviruses involve different pathways, but key roles are played by small RNA/RNA interference (RNAi) pathways [7,8,9,10], which have been shown to be a major innate antiviral immune response in mosquitoes against arboviruses of all families [11,12]

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