Abstract

The mosquito vector Aedes aegypti transmits arthropod-borne viruses (arboviruses) of medical importance, including Zika, dengue, and yellow fever viruses. Controlling mosquito populations remains the method of choice to prevent disease transmission. Novel mosquito control strategies based on genetically manipulating mosquitoes are being developed as additional tools to combat arbovirus transmission. Genetic control of mosquitoes includes two basic strategies: population suppression and population replacement. The former aims to eliminate mosquito populations while the latter aims to replace wild populations with engineered, pathogen-resistant mosquitoes. In this review, we outline suppression strategies being applied in the field, as well as current antiviral effector genes that have been characterized and expressed in transgenic Ae. aegypti for population replacement. We discuss cutting-edge gene drive technologies that can be used to enhance the inheritance of effector genes, while highlighting the challenges and opportunities associated with gene drives. Finally, we present currently available models that can estimate mosquito release numbers and time to transgene fixation for several gene drive systems. Based on the recent advances in genetic engineering, we anticipate that antiviral transgenic Ae. aegypti exhibiting gene drive will soon emerge; however, close monitoring in simulated field conditions will be required to demonstrate the efficacy and utility of such transgenic mosquitoes.

Highlights

  • Arthropod-borne viruses, including Zika (ZIKV), dengue (DENV), chikungunya (CHIKV), and yellow fever viruses (YFV), are emerging global health threats that have recently exhibited resurgence in prevalence [1]

  • DENV3 (~10% infection prevalence), but were unable to affect CHIKV replication [35]. These results suggest that DENV3 may be more vulnerable to miRNA-mediated silencing than CHIKV

  • Compensate for any loss of fitness associated with the effector gene; Link tightly to complex effector genes that are associated with a fluorescent marker; Drive the effector gene relatively quickly to fixation within the target population; Adapt to genetically diverse strains of mosquitoes; Remain confined to the targeted species irrespective of population structure and mating dynamics between species; Resist mutations that diminish or block drive to be sustained in nature; Be socially accepted by those communities who might benefit

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Summary

Introduction

Arthropod-borne viruses (arboviruses), including Zika (ZIKV), dengue (DENV), chikungunya (CHIKV), and yellow fever viruses (YFV), are emerging global health threats that have recently exhibited resurgence in prevalence [1]. Controlling Ae. aegpyti populations to limit human exposure to infected vectors is currently the method of choice to prevent arboviral disease transmission. In the context of vector control, genetic pest management is aiming at (1) eliminating insect populations by inducing lethality or sterility (population suppression) or (2) replacing wild-type populations with transgenic insects that have been engineered to be resistant to pathogen infection/transmission (population replacement). These techniques may involve the introduction/overexpression (gain-of-function) or disruption (loss-of-function) of gene(s) associated with essential cellular or pathogen pathways, host immunity, sex determination, fecundity, or reproduction

Aedes aegypti Population Suppression Strategies
Antiviral Effector Strategies for Aedes aegypti Population Replacement
Method
Gene Drive Principles
Gene Drive Technologies for Aedes aegypti
Aedes aegypti Population Replacement Models
Findings
Conclusions

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