Metabolic basis of mosquito-endosymbiont-virus interactions

项目概要/摘要 AE.自然界中的埃及伊蚊在其对病毒的媒介能力（蚊子的放任性）方面有很大的不同。 感染并传播病毒）。病毒的成功传播主要取决于其 克服感染和逃避由共感染病原体或共存共生体施加的障碍的能力， 蚊子。病毒是专性寄生虫，因此，必须主要竞争资源（或营养） 在复制的初始部位中肠因此，它们引起蚊子代谢的显著变化， 环境，以利于病毒复制的需要。代谢环境（称为代谢组）可以 可以精确测量，并直接与复制和传播水平相联系，因此可以用来控制 这些事件。在这个项目中，我们将确定是否操纵蚊子的代谢环境， 干扰病毒复制的成功，通过创造代谢阻塞点，限制病毒的传播， 病毒从载体。我们还将评估Wolbachia（一种具有阻断病毒的能力的内共生体） 传播）可能竞争或限制病毒复制所需的代谢资源，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 天然的或人工的手段）来创造用于病毒复制和传播的难治环境。这项工作将 也为代谢重编程和其他重要的 病媒的表型，如杀虫剂抗性、种群结构和地理分布，以及 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.