Controlling Arbovirus Transmission: PopulationSuppression and Virus-Induced Mosquito Death

摘要： 伊蚊继续传播登革热、寨卡病毒和黄热病等病毒，世界上大部分地区都有 处于危险之中的人群。在登革热疫情持续、寨卡病毒肆虐的巴西尤其如此。 流行病打击最严重，城市黄热病不断有重新出现的危险。为了建立新 病媒控制战略，巴西率先测试并批准了一项名为“释放病毒”的新战略 显性致死性昆虫 (RIDL)，基于 Oxitec, LLC 的知识产权。 RIDL 依赖于 大量释放雄性 Ae。埃及蚊子；与野生雌性交配会产生晚期幼虫死亡的后代 或蛹。虽然实地试验已证明种群抑制取得了成功，但大范围推广仍面临障碍。 该技术的使用包括监测难度、释放雄性的竞争力、使用抗生素的成本 在工厂规模抑制致命表型，释放后蚊子数量迅速恢复 停止。模型表明，在种群抑制后，抗病原体蚊子的释放 运动可以导致耐药表型的建立，即所谓的“减少和替代”方法 这可以更永久地阻止传输。开发减少和替换系统来控制 登革热/寨卡病毒传播，伊蚊中的转基因条件不育系统。 aegypti 将成立（目标 1）。 与目前的方法不同的是，工厂规模的饲养被释放的雄性必须在存在的情况下进行 四环素，这种方法只需要在产蛋群体中使用抗生素，基本上 降低成本。早期胚胎致死率将反过来简化监测方法。该项目还将开发 感染后死亡的伊蚊菌株。埃及伊蚊将为所有蚊媒提供广泛的抵抗力 黄病毒（目标 2）。这种创新方法利用了在导航方面已经取得的进展 转基因Ae。埃及伊蚊通过巴西监管程序，预计将开发的产品 在这项工作结束时直接进入现场测试的风险评估流程。

Abstract: Aedes mosquitoes continue to transmit viruses such as dengue, Zika and yellow fever, with much of the world’s population at risk. This is particularly true in Brazil, where dengue epidemics are continuous, where the Zika epidemic hit hardest, and where urban yellow fever continually threatens to re-emerge. In order to establish new vector control strategies, Brazil has pioneered the testing and approval of a new strategy called Release of Insects with Dominant Lethality (RIDL), based on the intellectual property of Oxitec, LLC. RIDL relies on the mass release of male Ae. aegypti mosquitoes; mating with wild females results in progeny that die as late larvae or pupae. While field trials have demonstrated successful population suppression, obstacles to the widespread use of the technology include difficulty in monitoring, competitiveness of released males, cost of antibiotic used to suppress the lethal phenotype at factory scale, and rapid recovery of the mosquito population once releases cease. Modeling suggests that the release of pathogen-resistant mosquitoes following a population suppression campaign can result in the establishment of the resistance phenotype, a so called “reduce and replace” approach that could more permanently block transmission. To develop a reduce and replace system for the control of dengue/Zika transmission, a transgenic conditional sterility system in Ae. aegypti will be established (Aim 1). Unlike current approaches where factory-scale rearing of released males must occur in the presence of tetracycline, such an approach necessitates antibiotic use only in the egg production colony, substantially reducing costs. Early embryonic lethality will in turn simplify monitoring approaches. This project will also develop a death-upon-infection strain of Ae. aegypti that will provide broad resistance across all mosquito-borne flaviviruses (Aim 2). This innovative approach takes advantage of progress already made in navigating transgenic Ae. aegypti through the regulatory process in Brazil, and the products to be developed are anticipated to directly enter the risk assessment process for field-based testing at the conclusion of this work.