Controlling Arbovirus Transmission: PopulationSuppression and Virus-Induced Mosquito Death

控制虫媒病毒传播：种群抑制和病毒引起的蚊子死亡

• 批准号: 9890195
• 负责人: Zach N. Adelman
• 金额: $ 15.04万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-13 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9890195
• 关键词: Adolescent; Adult; Aedes; Aedes aegypti genome; Americas; Antibiotics; Arbovirus Infections; Arboviruses; Automobile Driving; Brazil; Breeding; Cell Culture System; Cessation of life; Chemicals; Cleaved cell; Contracts; Country; Culicidae; Dengue; Dengue Fever; Development; Disease Outbreaks; Embryo; Environmental Impact; Epidemic; Female; Fertility; Flavivirus; Florida; Genes; Goals; Homing; Human; Infection; Insecta; Insecticides; Intellectual Property; Larva; Location; Modeling; Monitor; Mosquito Control; Neurotoxins; Partner in relationship; Peptide Hydrolases; Peptides; Phenotype; Population; Population Control; Populations at Risk; Privatization; Process; Process Assessment; Production; Proteins; Public Health; Pupa; Recovery; Reporting; Resistance; Resources; Ribosomal DNA; Risk; Risk Assessment; Series; Site; Source; Sterility; System; Technology; Testing; Testis; Tetracycline Control; Tetracyclines; Texas; Time; Transgenes; Transgenic Organisms; Universities; Vaccines; Viral; Virus; Virus Replication; Work; Yellow Fever; ZIKA; Zika Virus; base; cost; egg; endonuclease; experience; fitness; improved; innovation; malaria mosquito; male; mortality; mosquito-borne; negative affect; new technology; next generation; nuclease; pathogen; programs; sperm cell; sperm viability; success; survivorship; transmission process; vector; vector control; vector mosquito; viral transmission; zika fever

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.

抽象的： 艾德斯蚊子继续传播登革热，寨卡和黄热等病毒，世界上大部分地区的大部分 人口有风险。在巴西尤其如此，在巴西，球迷是连续的，寨卡 流行病最大，城市黄热病不断威胁重新出现。为了建立新 矢量控制策略，巴西率先确定了一项新策略的测试和批准，称为释放 基于Oxitec，LLC的知识产权，具有占主导地位的昆虫（RIDL）。里德依靠 男性AE的群众释放。埃及蚊子；与野生女性交配导致进展，死于幼虫 或p。虽然现场试验表现出成功的人口抑制，但宽度的障碍 该技术的使用包括难以监测，释放男性的竞争力，使用的抗生素成本 抑制工厂规模的致命表型，并释放蚊子的迅速恢复 停止。建模表明，种群抑制后，抗病原理的蚊子的释放 运动可以导致建立抵抗表型，这就是所谓的“减少和替换”方法 这可以更永久地阻止传输。开发减少和替换系统以控制 登革热/Zika传播，AE中的转基因条件无菌系统。将建立埃及（AIM 1）。 与当前的方法不同，在存在的情况下，必须在发生工厂规模的饲养释放的男性 四环素，这种必要的方法仅在卵产生菌落中使用抗生素 降低成本。早期的胚胎致死性将依次简化监测方法。这个项目也将发展 AE的感染菌株。埃及将在所有蚊子传播中提供广泛的抵抗力 黄病毒（AIM 2）。这种创新的方法利用了导航中已经取得的进步 转基因AE。埃及通过巴西的监管过程，预计将要开发的产品 在这项工作结束时，直接输入基于现场测试的风险评估过程。