A look into the future: Using a transcriptomic meta-analysis ofDiptera-Wolbachiasystems to project the sustainability of arboviral control strategies

Abstract

BackgroundAn effective strategy for arboviral control consists in transfectingAedes aegyptimosquitoes with the intracellular bacteriaWolbachia pipientis, which reduces host viral susceptibility and spreads itself into wild populations via reproductive manipulations. However, the prospect of losing the efficacy of this strategy underscores the need for deepening the mechanistic knowledge ofDiptera-Wolbachiasystems and identifying relevantWolbachiaeffects that could decline upon adaptation ofA. aegyptitransfections. A systematic comparison of publicly availableDiptera-Wolbachiatranscriptomic datasets could yield progress in this matter.Methodology/Principal findingsWe derived differentially expressed gene (DEG) sets from previously publishedDiptera-Wolbachiatranscriptomic datasets, subjected them to enrichment analysis of Gene Ontology terms, and intersected the results to identify patterns of host gene/function regulation byWolbachia. A putative farnesoic acid methyl transferase (AAEL004667) and a flavin-containing monooxygenase (AAEL000834) were consistently upregulated in transfectedA. aegyptiand linked to cytoplasmic incompatibility and viral susceptibility, being proposed as novel targets of study. Genes implicated in viral blocking—GNBPA1,PGRPS1,DEFC,Tf1, serine-type endopeptidases and endopeptidase inhibitors— were consistently upregulated in transfectedA. aegyptibut not in native infections, indicating that they could lose responsiveness toWolbachiaover time and should be considered to keep the efficacy of arboviral control. The commonality of chitinase regulation byWolbachiawas identified and proposed as an explanation for the loss of desiccation resistance in transfectedA. aegypti’s eggs, which is a main obstacle for the introgression ofWolbachiain mosquito populations.Conclusions/SignificanceThe present work points out relevant gene targets to consider for arboviral control sustainability and provides new hypotheses for deepening the understanding ofDiptera-Wolbachiasystems.Author SummaryArboviral diseases (e.g. dengue), which are mainly transmitted by the mosquitoAedes aegypti, impose a global public health crisis. An effective strategy for controlling the spread of these diseases is to artificially infectA. aegyptipopulations with the bacteriaWolbachia pipientis, which reduces its capacity to transmit arboviruses. However, future adaptive changes in the novelA. aegypti-Wolbachiaassociation could diminish the efficacy of this approach. To prevent this, it is crucial to have a solid biological understanding ofWolbachiainfections and predictions about specific changes that artificial infections could undergo. By analyzing publicly available biological data fromWolbachia-infected mosquitoes and flies we were able to propose new hypotheses regarding general aspects ofWolbachiainfection and to identify antiviral effects ofWolbachiainA. aegyptithat could decline over time, thus providing relevant information for keeping sustainability of a key arboviral control strategy.