Passerine filariasis and West Nile virus transmission

描述（申请人提供）：在自然界中，虫媒病毒的脊椎动物宿主通常携带寄生虫，包括微丝蚴。实验室研究表明，蚊子同时摄入微丝蚴和虫媒病毒可显著提高 与单独摄入相同剂量的虫媒病毒相比，这是因为当微丝蚴被摄入时，它们可以穿透蚊子的中肠，并允许病毒立即传播到蚊子的体腔中。这增加并加速了蚊子的病毒感染性，并可能产生两个重要的流行病学后果。首先，由于对病毒感染性的中肠屏障，通常对病毒感染难治的蚊子物种现在可能发生感染。这可以增加参与病毒传播周期的次级媒介物种的数量和重要性。其次，微丝蚴增强可以加速蚊子体内的病毒发展，缩短蚊子成为传染性所需的时间（=外源性潜伏期[EIP]）。EIP的小幅减少可以导致向量容量的大幅增加。这种现象被称为“微丝蚴增强虫媒病毒传播”，并已使用几个人工设计的模型系统进行了验证。然而，微丝蚴增强从未被测试使用自然发生的地方性虫媒病毒传播系统。这就是本提案的目的。在北美，鸣禽体内寄生着多种丝虫，通常流行率很高。鸣禽对某些虫媒病毒的地方性维持也很重要，如西尼罗河病毒（WNV）。这一建议的假设是，在鸣禽微丝蚴感染可能会增强通过地方病蚊子载体，库蚊传播西尼罗河病毒。为了检验这一假设，将比较以双重感染的鸟类（即，西尼罗河病毒加微丝蚴）与单感染禽的比较 (i.e.,仅WNV）。该实验将量化双重感染对随后1）蚊子内的病毒传播率，2）蚊子传播WNV的速率，3）蚊子内WNV的外源性潜伏期，和4）蚊子的每日存活率的影响。这些研究的结果将确定双重感染的鸣禽是否比单一感染的鸣禽更能增强病毒对蚊子的传播。如果是这样的话，这就有可能在一个给定的有WNV能力的鸟类种群中，那些有活跃微丝蚴感染的个体可能构成潜在的“超级”微丝蚴亚群。 发射机”。意义没有一个更全面的了解微丝蚴增强在自然发生的系统中的潜在作用，神秘的，潜在的重要放大主机和载体可能会被忽视，我们的了解虫媒病毒的地方性传播可能是不完整的。

DESCRIPTION (provided by applicant): In nature, vertebrate hosts of arboviruses often harbor parasites, including microfilariae. Laboratory studies have shown that concurrent ingestion of microfilariae and arboviruses by mosquitoes can result in significantly more efficient transmission of the arbovirus than when the same dose of arbovirus is ingested alone. That is because when microfilariae are ingested, they can penetrate the mosquito midgut and allow immediate dissemination of virus into the mosquito body cavity. This increases and accelerates viral infectivity of mosquitoes and can have 2 important epidemiological consequences. First, mosquito species that are normally refractory to viral infection because of midgut barriers to vira infectivity may now develop infections. This can increase the number and importance of secondary vector species involved in a virus transmission cycle. Second, microfilarial enhancement can accelerate viral development within the mosquito, shortening the time required for mosquitoes to become infectious (=extrinsic incubation period [EIP]). Small reductions in EIP can lead to large increases in vectorial capacity. This phenomenon is called "microfilarial enhancement of arboviral transmission" and has been validated using several artificially contrived model systems. However, microfilarial enhancement has never been tested using a naturally-occurring enzootic arboviral transmission system. That is what this proposal intends to do. In North America, songbirds harbor a diversity of filarial parasites, often at very high prevalence. Songbirds are also important for the enzootic maintenance of certain arboviruses, such as West Nile virus (WNV). The hypothesis of this proposal is that the microfilarial infections in songbirds may enhance WNV transmission by the enzootic mosquito vector, Culex pipiens. To test the hypothesis, infection outcomes will be compared between mosquitoes fed on dually infected birds (i.e., WNV plus microfilariae) versus singly infected birds (i.e., WNV only). The experiments will quantify the effect that dual infections have on the subsequent 1) viral dissemination rate within mosquitoes, 2) rate of WNV transmission by mosquitoes, 3) extrinsic incubation period of WNV within mosquitoes, and 4) daily survivorship of mosquitoes. The results of these studies will determine whether dually infected songbirds enhance virus transmission to mosquitoes compared with that of singly infected songbirds. If so, this opens the possibility that within a given population of WNV-competent bird species, those individuals with active microfilarial infections may constitute a subpopulation of potential "super transmitters". Significance. Without a fuller understanding of the potential role of microfilarial enhancement in naturally occurring systems, cryptic, potentially important amplifying hosts and vectors may be overlooked and our understanding of enzootic transmission of arboviruses may be incomplete.