Abstract
Dengue virus (DENV) is a mosquito-transmitted virus imposing a significant burden on human health around the world. Since current control strategies are not sufficient, there is an urgent need to find alternative methods to control DENV transmission. It has been demonstrated that introduction of Wolbachia pipientis in Aedes aegypti mosquitoes can impede DENV transmission with the mechanism(s) not fully understood. Recently, a number of studies have found the involvement of chromodomain DNA binding helicases in case of Human Immunodeficiency virus (HIV) and Influenza A virus infection. In this study, we have identified three chromodomain helicase DNA binding protein (CHD) genes in Ae. aegypti and looked at their response in the case of Wolbachia and DENV infections. Foremost amongst them we have found that AeCHD7/Kismet is significantly downregulated in the presence of Wolbachia infection only in female mosquitoes. Furthermore, AeCHD7 levels showed significant increase during DENV infection, and AeCHD7 depletion led to severe reduction in the replication of DENV. Our data have identified AeCHD7 as a novel Ae. aegypti host factor that is important for DENV replication, and Wolbachia downregulates it, which may contribute towards the mechanism(s) of limiting DENV replication.
Highlights
Among arboviruses, dengue virus (DENV) is one of the most important flaviviruses having the potential to affect two-thirds of the world’s population[1,2]
Blastp was run to identify their homologs in D. melanogaster and Culex quinquefasciatus, and these were determined as AeCHD1 (AAEL004716) having 58% identity with D. melanogaster CHD1 protein (NP_477197.1), AeCHD3 (AAEL013136) that showed 70% identity with D. melanogaster CHD3 protein (AAD17276.1) and AeCHD7 (AAEL002230) showing 58% identity with D. melanogaster Kismet/CHD7 protein (NP_001245820.1). qPCR primers were designed for all the three AeCHD family members to experimentally validate their expression in Ae. aegypti mosquitoes by RT-qPCR, and the effect of Wolbachia infection on their expression level
RT-qPCR results were further validated with plaque assay, which confirmed reduction in Dengue virus (DENV) virion production in AeCHD7 knocked down cells as compared with dsGFP or mock-transfected Aa20 cells (Fig. 5C). These results indicate that AeCHD7 is a host factor that is used by DENV to facilitate its replication in Ae. aegypti female mosquitoes, and Wolbachia downregulates AeCHD7 as shown above, which may contribute to restricting DENV replication
Summary
Dengue virus (DENV) is one of the most important flaviviruses having the potential to affect two-thirds of the world’s population[1,2]. DENV is primarily transmitted to humans through the bit of mosquito vector Aedes aegypti, leading to dengue infection and potentially dengue haemorrhagic fever[3,4,5]. In order to exploit Wolbachia’s potential to limit arbovirus transmission, three strains of Wolbachia, wAlbB (from Ae. albopictus)[16], wMel (from Drosophila melanogaster)[17] and wMelPop-CLA (from D. melanogaster)[18] have been successfully transinfected into Ae. aegypti Among these three strains, wMel and wMelPop-CLA are the most promising ones for virus blocking[7,8,9,10,19,20]. We have identified functional homologs of the CHD family members in Ae. aegypti and looked at the effect of Wolbachia infection on their expression. This study will help to understand the role of AeCHD7 in DENV-Aedes-Wolbachia interactions
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