Consequences of pathogen co-infection in mosquitoes on West Nile virus transmission

项目总结/摘要 西尼罗河病毒（West Nile virus，WNV）在除南极洲以外的各大洲肆虐， 广泛分布的人畜共患节肢动物传播病毒（虫媒病毒）， 自1999年以来，美国有78万人患病，1,549人死亡。WNV保持 在库蚊和鸟类地方性传播周期中， 一系列其他寄生虫和病原体因此，库蚊负责 人的地方性传播和桥梁传播经常暴露于 各种各样的寄生虫和病原体。此前的研究表明， 昆虫中多种病原体的感染可导致直接的和免疫介导的 交互.在蚊子中，这些相互作用可能对 虫媒病毒复制和感染唾液腺的能力（即载体 能力）。此外，合并感染可能会影响生存或所需的时间， 病毒到达唾液腺（即外源性潜伏期）， 模型中的重要参数，用于描述暴露给 病原体通过指定的蚊子种群/感染宿主每天（即媒介 能力）。该提案的目标是1）评估病原体的后果 WNV载体能力和载体容量的相互作用和2）应用 流行病学模型，以评估共同循环的寄生虫影响 西尼罗河病毒在自然界中的繁殖数（R 0）。利用实验室感染实验， 库蚊，我们将测试的假设，共同感染疟原虫或 昆虫特异性黄病毒将显著增加或降低WNV载体能力。 在完成这些研究后，我希望能够确定具体的共同点， 对西尼罗河病毒传播有重要影响的循环病原体， 自然虽然这些常见的寄生虫和病原体可能不会直接引起人类 疾病，我预计强调这些病原体影响人类健康的潜力 间接地，通过驱动WNV的动力学。在此期间，首席研究员 (PI)将接受病毒学、载体能力和数学方面的结构化培训， 建模，然后将这些技能应用到这里概述的研究。这个奖项将 提供一个基础，帮助PI实现他的职业目标， 虫媒病毒传播机制，以制定更好的干预措施， 减轻人类和动物疾病。

PROJECT SUMMARY/ABSTRACT Occurring on every continent except Antarctica, West Nile virus (WNV) is the most widely distributed zoonotic arthropod-borne virus (arbovirus) resulting in an estimated 780,000 human illnesses and 1,549 deaths in the U.S. since 1999. WNV is maintained in a Culex mosquito and bird enzootic transmission cycle which is the same cycle for a suite of other parasites and pathogens. As a result, the Culex mosquitoes responsible for enzootic transmission and bridge transmission to humans are frequently exposed to a variety of other parasites and pathogens. Prior studies have demonstrated that co- infections of multiple pathogens in insects can result in direct and immune-mediated interactions. In mosquitoes, these interactions could have important consequences on the ability of an arbovirus to replicate and infect the salivary glands (i.e. vector competence). Additionally, co-infections could influence survival or the time it takes for the virus to reach the salivary glands (i.e. extrinsic incubation period) which are important parameters in the model that describes the number of new hosts exposed to a pathogen by a specified population of mosquitoes per infected host per day (i.e. vectorial capacity). The goal of this proposal is to 1) evaluate the consequences of pathogen interactions on WNV vector competence and vectorial capacity and 2) apply epidemiological models to assess the ability of co-circulating parasites to impact the reproductive number (R0) of WNV in nature. Using laboratory infection experiments in Culex mosquitoes, we will test the hypothesis that co-infections with Plasmodium or an insect-specific flavivirus will significantly increase or decrease WNV vectorial capacity. At the completion of these studies, it is my expectation to have identified specific co- circulating pathogens that have important consequences for WNV transmission in nature. Although these common parasites and pathogens may not directly cause human disease, I anticipate highlighting the potential for these pathogens to affect human health indirectly, by driving dynamics of WNV. During this award, the Principal Investigator (PI) will receive structured training in virology, vector competence, and mathematical modeling and will then apply those skills to the research outlined here. This award will provide a foundation to help the PI achieve his career goals of understanding mechanisms of arboviral transmission to develop improved interventions aimed at mitigating human and animal disease.