Metabolic basis of mosquito-endosymbiont-virus interactions

项目概要/摘要 艾。自然界中的埃及伊蚊在其传播病毒的载体能力方面存在显着差异（蚊子的许可性） 被感染，然后传播病毒）。病毒的成功传播关键取决于其 克服感染和逃避由共同感染病原体或共生共生体所造成的障碍的能力 蚊子。病毒是专性寄生虫，因此必须主要竞争资源（或营养物质） 在复制的初始位点，中肠。因此，它们会引起蚊子代谢的显着变化 有利于病毒复制需求的环境。代谢环境（称为代谢组）可以 可以精确测量并与复制和传播水平直接相关，从而用于控制 这些事件。在这个项目中，我们将确定操纵蚊子的代谢环境是否可以 通过创建代谢阻塞点来限制病毒的传播，从而干扰病毒复制的成功 来自载体的病毒。我们还将评估沃尔巴克氏体（一种能够阻断病毒的内共生体）如何 传播）可能会竞争或限制病毒复制所需的代谢资源，并且如果这种“病原体” “阻断”表型取决于其在蚊子内的密度。我们还将确定病毒是否以及如何 对抗沃尔巴克氏体或其他代谢干扰的影响，以产生抵抗力或逃避代谢 压力。通过这项工作，我们将确定如何利用载体的代谢环境（通过 自然或人工手段）创造病毒复制和传播的难熔环境。这项工作将 还为发展代谢重编程和其他重要的关联提供了基础 媒介表型，例如杀虫剂抗性、种群结构和地理分布以及一般情况 蚊子生物学，所有这些都是媒介能力和病原体传播的主要决定因素。

PROJECT SUMMARY / ABSTRACT Ae. aegypti in nature differs dramatically in its vector competence for viruses (the permissiveness of the mosquito to become infected and to then transmit the virus). Successful transmission of a virus critically depends on its ability to overcome infection and escape barriers imposed by co-infecting pathogens or co-habiting symbionts in the mosquito. Viruses are obligate parasites and therefore, must compete for resources (or nutrients) primarily at the initial site of replication, the midgut. Thus, they induce significant changes in the mosquito metabolic environment to benefit viral replicative needs. The metabolic environment (referred to as the metabolome) can be precisely measured and directly linked to the level of replication and transmission and thus exploited to control these events. In this project we will determine if manipulating the metabolic environment of the mosquito can interfere with the success of viral replication by creating metabolic choke-points that limit transmission of the virus from the vector. We will also evaluate how Wolbachia (an endosymbiont that has the ability to block virus transmission) might compete for or limit metabolic resources required for virus replication and if this `pathogen- blocking' phenotype is dependent on its density within the mosquito. We will also identify if and how viruses will counter the effects of Wolbachia or other metabolic interference to develop resistance or escape metabolic pressure. Through this work, we will identify how the metabolic environment of the vector can be exploited (by natural or artificial means) to create refractory environments for viral replication and transmission. This work will also provide a foundation for developing associations between metabolic reprogramming and other important vector phenotypes, such as insecticide resistance, populations structure and geographic distribution, and general mosquito biology, all of which are major determinants of vectorial capacity and pathogen transmission.