Metabolic basis of mosquito-endosymbiont-virus interactions

蚊子-内共生体-病毒相互作用的代谢基础

• 批准号: 10574484
• 负责人: Rushika Perera
• 金额: $ 53.15万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574484
• 关键词: Acute; Aedes; Arboviruses; Bacteria; Biochemical Pathway; Biological; Biology; Blood Vessels; Cell Culture Techniques; Chikungunya fever; Choking; Country; Culicidae; Dengue Fever; Dengue Hemorrhagic Fever; Dengue Shock Syndrome; Dengue Virus; Energy Metabolism; Ensure; Environment; Event; Extravasation; Family; Fever; Flaviviridae; Foundations; Genome; Geographic Distribution; Heritability; Human; In Vitro; Infection; Insecta; Insecticide Resistance; Life; Life Cycle Stages; Link; Lipids; Lipolysis; Maintenance; Marketing; Measures; Mediating; Membrane; Metabolic; Metabolic Pathway; Metabolism; Midgut; Modeling; Nature; Nutrient; Parasites; Pathway interactions; Persons; Phenotype; Population; RNA Viruses; Refractory; Resistance development; Resources; Risk; Serotyping; Site; Sphingolipids; Structure; Syndrome; Therapeutic; Tissues; Translations; Vaccinee; Vaccines; Vectorial capacity; Viral; Viral Load result; Viral Physiology; Viral Proteins; Virion; Virus; Virus Replication; Wolbachia; Work; World Health Organization; Yellow Fever; antagonist; density; disease transmission; endosymbiont; fitness; lipid biosynthesis; metabolic phenotype; metabolome; mitochondrial metabolism; novel; novel strategies; pathogen; permissiveness; pressure; success; symbiont; transmission process; vector; vector competence; vector mosquito; vector transmission; viral resistance; viral transmission; zika fever

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.

项目摘要 /摘要 Ae。自然界中的埃及在其病毒的矢量能力上有很大差异（蚊子的允许性 被感染并传播病毒）。成功传播病毒取决于其 通过共同感染病原体或共生共生体中的感染和逃避障碍的能力 蚊子。病毒是强制的寄生虫，因此必须主要争夺资源（或营养） 在复制的最初位置，中肠。因此，它们引起了蚊子代谢的重大变化 有益于病毒复制需求的环境。代谢环境（称为代谢组）可以 精确测量并直接链接到复制和传输水平，从而利用 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可以 通过创建限制传播的代谢扼流点来干扰病毒复制的成功 载体的病毒。我们还将评估Wolbachia如何（一种具有阻断病毒的内共生体 传播）可能会争夺病毒复制所需的代谢资源或限制该病原体 - 阻塞的表型取决于其在蚊子内的密度。我们还将确定是否以及病毒将如何 应对Wolbachia或其他代谢干扰的影响，以发展抗药性或逃脱代谢 压力。通过这项工作，我们将确定如何利用向量的代谢环境（通过 自然或人工手段）创建用于病毒复制和传播的难治性环境。这项工作将 还为建立代谢重编程与其他重要重要的建立关联提供了基础 矢量表型，例如杀虫剂的耐药性，人口结构和地理分布，一般 蚊子生物学，所有这些都是媒介物能力和病原体传播的主要决定因素。