Zika virus evolutionary dynamics in host adaptation

寨卡病毒宿主适应的进化动力学

• 批准号: 9329778
• 负责人: Matthew T Aliota
• 金额: $ 22.95万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-07 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9329778
• 关键词: Address; Aedes; Africa; Americas; Anatomy; Arboviruses; Arthropods; Bacteria; Biocontrols; Biological; Blood Circulation; Brazil; Chikungunya virus; Clinical; Coitus; Colombia; Congenital Abnormality; Culicidae; Dengue; Dengue Virus; Disease; Disease Outbreaks; Effectiveness; Entomology; Event; Evolution; Federated States of Micronesia; Fever; Flavivirus; French Polynesia; Future; Genetic Variation; Goals; Horizontal Disease Transmission; Human; Infection; Insecta; Intervention; Island; Laboratories; Laboratory Study; Link; Locales; Maintenance; Mediating; Methods; Modeling; Mus; Mutation; Neurologic; Oceania; Outcome; Pathway interactions; Pattern; Perinatal; Perinatal Infection; Phenotype; Population; Population Heterogeneity; Prevention; Public Health; RNA Viruses; Readiness; Recording of previous events; Reporting; Resistance; Route; Serial Passage; Shapes; South America; Syndrome; Testing; Time; Translating; United States National Institutes of Health; Variant; Virus; Virus Diseases; Wolbachia; Yellow fever virus; Zika Virus; arbovirus disease; cost; global health; improved; invertebrate host; laboratory experiment; member; novel strategies; pathogen; peri-urban; pressure; prevent; programs; response; tool; transmission process; viral transmission; virology; virus genetics

PROJECT SUMMARY The project goal is to understand the selective pressures associated with Zika virus (ZIKV) adaptation. New approaches to preventing ZIKV are needed because the endemic range of this virus is expanding and because current methods are limited to controlling mosquito populations, and they cannot prevent invasion of this virus into new locales. A promising candidate for arbovirus control and prevention relies on the introduction of the intracellular bacterium Wolbachia into Ae. aegypti mosquitoes. Wolbachia biocontrol has advanced from laboratory experiments demonstrating that Wolbachia reduces the transmission potential of Ae. aegypti for certain viruses to small-scale field trials demonstrating that Wolbachia are capable of spreading through wild Ae. aegypti populations. This primarily has been proposed as a tool to control dengue virus (DENV) transmission; however, Wolbachia infections confer protection for their insect hosts against a range of pathogens including for Ae. aegypti against ZIKV. A critical next step is to assess the impact of Wolbachia on virus evolution to determine whether or not Wolbachia biocontrol is a sustainable method for ZIKV control and prevention that will not be undermined by mosquito or virus evolution. Likewise, alternative transmission pathways for ZIKV (e.g., sexual intercourse and perinatal transmission) are creating a scenario by which a highly mutable RNA virus could readily exploit new routes of transmission during circulation in South America. Accordingly, through this NIH/NIAD R21 we will perform experimental evolution studies to evaluate and anticipate evolutionary changes of ZIKV- Wolbachia-mosquito interactions and vertebrate co-adaptation. Furthermore, Wolbachia-infected Ae. aegypti colonies have been established by a complementary Eliminate Dengue Program (EDP) project in Colombia to evaluate the impact of Wolbachia biocontrol on DENV transmission. There are two specific aims 1.) Evaluate the impact of Wolbachia-infected Ae. aegypti on ZIKV transmission potential and 2.) Evaluate the consequences of releasing ZIKV from alternate cycling between vertebrate and invertebrate hosts. Experimental evolution of ZIKV via alternate passage between Wolbachia-infected mosquitoes and mice is new. Medium-scale Wolbachia deployments have commenced or are imminent. Therefore, assessing the evolutionary potential of ZIKV to adapt to Wolbachia-infected Ae. aegypti will help inform the viability of Wolbachia biocontrol for ZIKV control. Potentially, through this R21, valuable evidence could be provided that justifies expanding this type of control program to other Ae. aegypti-transmitted arboviruses, e.g., ZIKV. And understanding the potential for new transmission pathways will be critically important for prediction, prevention, and control of this emerging viral disease.

项目摘要 该项目的目标是了解与寨卡病毒（ZIKV）适应相关的选择压力。新 需要预防ZIKV的方法，因为这种病毒的流行范围正在扩大， 目前的方法仅限于控制蚊子数量，不能防止这种病毒的入侵 进入新的区域虫媒病毒控制和预防的一个有希望的候选者依赖于引入 细胞内细菌Wolbachia转化为Ae.埃及蚊子。沃尔巴克氏体生物防治已经从 实验室实验表明，沃尔巴克氏体降低了Ae的传播潜力。埃及森林 某些病毒的小规模田间试验表明，沃尔巴克氏体能够通过野生Ae。 埃及人。这主要被提议作为控制登革热病毒（DENV）传播的工具; 然而，沃尔巴克氏体感染使其昆虫宿主免受一系列病原体的侵害， AE.埃及对ZIKV。下一步的关键是评估沃尔巴克氏体对病毒进化的影响，以确定 沃尔巴克氏体生物防治是否是ZIKV控制和预防的可持续方法， 被蚊子或病毒的进化所破坏。同样，ZIKV的替代传播途径（例如，性 性交和围产期传播）正在创造一种情况，通过这种情况，高度变异的RNA病毒可以很容易地 在南美洲的传播过程中利用新的传播途径。因此，通过这个NIH/NIAD R21 我们将进行实验性进化研究，以评估和预测ZIKV的进化变化- 沃尔巴克氏体-蚊子相互作用和脊椎动物的共同适应。此外，Wolbachia感染的Ae. aegypti 哥伦比亚的一个补充性的消灭登革热计划（EDP）项目已经建立了一些殖民地， 评估Wolbachia生物防治对DENV传播的影响。具体目标有两个：（1）评价 Wolbachia感染的Ae.埃及伊蚊对ZIKV传播潜力的影响，以及2.）评估后果 从脊椎动物和无脊椎动物宿主之间的交替循环中释放ZIKV。实验进化 ZIKV通过Wolbachia感染的蚊子和小鼠之间的交替传代是新的。中型沃尔巴克氏体 部署已经开始或即将开始。因此，评估ZIKV适应的进化潜力 感染沃尔巴克氏体的Ae.埃及伊蚊将有助于告知沃尔巴克氏体生物控制用于ZIKV控制的可行性。 通过这项R21，可能会提供有价值的证据，证明扩大这种控制是合理的 其他的Ae。埃及传虫媒病毒，例如，ZIKV。并了解新的 传播途径对于预测、预防和控制这种新兴病毒至关重要。 疾病