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经常寄生寄生虫，包括微丝虫。实验室研究表明，蚊子同时摄取微丝虫和虫媒病毒可以显著提高效率。 虫媒病毒的传播比同样剂量的虫媒病毒单独摄入时要好。这是因为当微丝虫被摄入时，它们可以穿透蚊子的中肠，使病毒立即传播到蚊子的体腔中。这会增加和加速蚊子的病毒感染性，并可能产生两个重要的流行病学后果。首先，由于病毒感染性的中肠屏障，通常对病毒感染具有抵抗力的蚊子物种现在可能会感染。这可能会增加病毒传播周期中涉及的次级媒介物种的数量和重要性。第二，微丝虫病的加强可以加速病毒在蚊子体内的发展，缩短蚊子感染所需的时间(=外部潜伏期[EIP])。弹性公网IP的小幅减少可以导致矢量容量的大幅增加。这种现象被称为“虫媒病毒传播的微丝虫病增强”，并已使用几个人工设计的模型系统进行了验证。然而，微丝虫病的增强从未使用自然发生的地方性虫媒病毒传播系统进行过测试。这就是这项提案想要做的。在北美，鸣禽栖息着各种各样的丝虫寄生虫，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，例如西尼罗河病毒(WNV)。这一建议的假设是，鸣禽中的微丝虫病感染可能会增强地方性蚊媒库蚊传播西尼罗河病毒的能力。为了验证这一假设，将比较以双重感染的鸟类(即西尼罗河病毒加微丝虫)为食的蚊子和单感染鸟类的蚊子的感染结果。 (即，仅限WNV)。这些实验将量化双重感染对随后的1)蚊子内病毒传播率，2)蚊子传播西尼罗河病毒的速度，3)西尼罗河病毒在蚊子内的外部潜伏期，以及4)蚊子每日存活率的影响。这些研究的结果将确定，与单一感染的鸣禽相比，双重感染的鸣禽是否会增强病毒对蚊子的传播。如果是这样的话，这就开启了一种可能性，即在西尼罗河病毒能胜任的鸟类的给定种群中，那些感染微丝虫病的个体可能构成潜在的“超级”亚群。 如果不能更充分地了解微丝虫病在自然发生的系统中的潜在作用，可能会忽视隐蔽的、潜在重要的放大宿主和载体，我们对虫媒病毒的地方性传播的理解可能不完整。

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.