Evolution of Chikungunya Virus in Wolbachia Infected mosquitoes

基孔肯雅病毒在沃尔巴克氏体感染的蚊子中的进化

• 批准号: 8873453
• 负责人: Jorge E Osorio
• 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: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8873453
• 关键词: Acute; Address; Aedes; Africa; Alphavirus; Americas; Arboviruses; Area; Arthritis; Bacteria; Biocontrols; Blood; Caribbean region; Cell Culture Techniques; Chikungunya virus; Chronic; Colombia; Competence; Culicidae; Dengue; Dengue Virus; Disease Outbreaks; Epidemic; Evolution; Future; Genetic; Goals; Growth; Human; Infection; Insecta; Intervention; Laboratories; Laboratory Study; Literature; Locales; Longevity; Maps; Mediating; Methods; Modeling; Mosquito Control; Mosquito-borne infectious disease; Mus; Mutation; Pathogenicity; Phenotype; Population; Prevention; Public Health; Reporting; Resistance; Risk; Role; Safety; Saliva; Southeastern Asia; Staging; Time; Togaviridae; United States; United States National Institutes of Health; Variant; Viral; Viremia; Virus; Virus Replication; Wolbachia; chikungunya; deep sequencing; feeding; mutant; novel strategies; pathogen; pressure; prevent; programs; public health relevance; research study; response; tool; transmission process; vector; virus genetics

 DESCRIPTION (provided by applicant): The project goal is to understand the selective pressures associated with Wolbachia-mosquito-Chikungunya virus (CHIKV) co-adaptation. New approaches to preventing CHIKV 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 shortens the lifespan of the mosquito while simultaneously reducing virus replication 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 CHIKV. 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 CHIKV control and prevention that will not be undermined by mosquito or virus evolution. Accordingly, through this NIH/NIAD R21 we will perform experimental evolution studies to evaluate and anticipate evolutionary changes of CHIKV-Wolbachia-mosquito interactions. 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 specific CHIKV phenotypes that arise during alternate passage between Wolbachia-infected Ae. aegypti and mice and 2.) Identify the genetic correlates of adaptation identified in Aim 1 and evaluate their role and importance in facilitating evolution in Wolbachia-infected Ae. aegypti. Experimental evolution of a CHIKV via alternate passage between Wolbachia-infected mosquitoes and mice is new. It is expected that medium-scale Wolbachia deployments will occur in the very near future. Therefore, assessing the evolutionary potential of CHIKV to adapt to Wolbachia-infected Ae. aegypti will help inform the viability of Wolbachia biocontrol for CHIKV 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., CHIKV.

 描述（由申请人提供）：该项目的目标是了解与沃尔巴克氏体-蚊子-基孔肯雅病毒 (CHIKV) 共同适应相关的选择压力，因为这种病毒的流行范围正在扩大，而且目前存在预防 CHIKV 的新方法。方法仅限于控制蚊子种群，并且无法阻止这种病毒侵入新的场所。虫媒病毒控制和预防的一个有希望的候选者依赖于细胞内的引入。细菌沃尔巴克氏体转化为埃伊菌。 沃尔巴克氏菌生物防治已从证明沃尔巴克氏菌缩短蚊子寿命的同时减少病毒复制到小规模田间试验，证明沃尔巴克氏菌能够在野生埃及伊蚊种群中传播。一种控制登革热病毒 (DENV) 传播的工具；然而，沃尔巴克氏体感染可以保护其昆虫宿主免受一系列病原体的侵害，包括埃及伊蚊。 CHIKV。下一步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一种不会受到蚊子或病毒进化破坏的可持续方法。 R21 我们将进行实验进化研究，以评估和预测 CHIKV-沃尔巴克氏体-蚊子相互作用的进化变化。已由哥伦比亚消除登革热计划 (EDP) 项目建立，旨在评估沃尔巴克氏体生物控制对 DENV 传播的影响。有两个具体目标 1.) 评估沃尔巴克氏体感染的伊蚊交替传代期间出现的特定 CHIKV 表型。埃及伊蚊和小鼠以及 2.) 确定目标 1 中确定的适应的遗传相关性，并评估它们在促进感染沃尔巴克氏体的伊蚊进化中的作用和重要性。通过感染沃尔巴克氏体的蚊子和小鼠进行 CHIKV 的实验进化是新的，预计在不久的将来将出现中等规模的沃尔巴克氏体部署，因此，评估 CHIKV 适应沃尔巴克氏体的进化潜力。感染埃及伊蚊将有助于了解沃尔巴克氏体生物防治 CHIKV 的可行性，通过这一 R21，可能会获得有价值的证据。前提是可以将这种类型的控制程序扩展到其他埃及伊蚊传播的虫媒病毒，例如 CHIKV。