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 面临危险的人口。在巴西尤其如此，那里的登革热疫情持续不断，寨卡病毒 疫情最严重，城市黄热病不断有再次出现的危险。为了建立新的 病媒控制战略，巴西率先测试和批准了一种名为释放的新战略 优势致死昆虫(RIDL)，基于Oxitec，LLC的知识产权。RIDL依赖于 大批量释放雄性Ae.埃及伊蚊；与野生雌性蚊子交配产生的后代会在幼虫晚期死亡 或者是蛹。虽然现场试验证明了成功的人口抑制，但普遍存在的障碍 该技术的使用包括监测困难、获释男性的竞争力、使用抗生素的成本 抑制工厂规模的致命表型，并在释放后迅速恢复蚊子种群 停止。模拟表明，在种群抑制之后，抗病原体蚊子的释放 运动可以导致抗性表型的建立，即所谓的“减少和替换”方法 这可能会更永久性地阻止传播。开发减少和替换系统以控制 登革热/寨卡病毒传播，一种转基因条件不育系统。将建立埃及人(目标1)。 与目前的方法不同的是，工厂规模的放生雄性饲养必须在 四环素，这样的方法只需要在鸡蛋生产群体中使用抗生素，基本上 降低成本。早期胚胎致死将反过来简化监测方法。这个项目也将发展 一种感染即致死的Ae.埃及伊蚊将在所有蚊媒传播的 黄病毒(目标2)。这种创新的方法利用了在导航方面已经取得的进展 转基因Ae.埃及伊蚊在巴西通过监管程序，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程序。

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.