Mechanisms of West Nile virus selection and strain displacement

项目摘要 研究拟解决PA-04 - 119生物防御和新兴传染病 疾病研究机会。西尼罗河病毒是NIAID B类优先病原体。的 在相对良好表征的时间和地点引入单一WNV菌株， 北美提供了一个独特的机会，可以前瞻性地研究 一种节肢动物传播的RNA病毒，因为它适应了一个天真的生态位。当WNV 在美洲仍然是一个相对同质的病毒群体，单一的基因型， 与引进的基因型不同的基因型已经在整个北方占主导地位。 自2002年以来，已经取代了美国以前存在的基因型 states.初步研究表明，这种新基因型的优势可能是 通过病毒和蚊子宿主之间的相互作用以及 与自然鸟类宿主的相互作用。一系列的生物机制可能导致 然而，一种虫媒病毒基因型与另一种虫媒病毒基因型的置换， 系统检查。因此，我们将检验一个优势的假设， WNV基因型可能是由于该基因型在蚊子中的选择优势 和/或禽类宿主。具体来说，拟议的研究将集中在这种优势是否是 通过遗传上确定的西尼罗河病毒株的差异潜力来实现：（a） 通过蚊子垂直传播并随后经口传播，（B）感染，产生 在生态相关的脊椎动物宿主中的病毒血症和病毒脱落。此外，我们建议 这些实验将确定这些表型差异是否与 在病毒复制事件中存在细胞水平的差异。最后，我们将确定 西尼罗河病毒传播周期中可能导致 观察到的一种病毒基因型的灭绝，因为它已被另一种取代， 虫媒病毒与脊椎动物和无脊椎动物宿主的相互作用 病毒传播的强度，从而改变了地方病扩增的速率， 病毒的遗传稳定性和随后的病毒适应性。这些研究的结果将 通过增加我们对选择性疾病的理解， 以西尼罗河病毒为模型，塑造侵入性媒介传播病毒种群的过程 用于将媒介传播的疾病因子引入未感染环境的系统。

Project Summary Research is proposed to address PA-04-119 Biodefense and Emerging Infectious Disease Research Opportunities. WNV is a NIAID Category B priority pathogen. The introduction of a single WNV strain at a relatively well characterized time and place in North America has provided a unique opportunity to prospectively study the evolution of an arthropod-transmitted RNA virus as it adapts to a na¿ve ecological niche. While WNV in the Americas remains a relatively homogeneous virus population, a single genotype that differs from the introduced genotype has become dominant throughout North America, and since 2002 has displaced previously existing genotypes in the United States. Preliminary studies suggest that the dominance of this new genotype may be facilitated by interactions between the virus and the mosquito host as well as by interactions with natural avian hosts. The range of biological mechanisms that may lead to the displacement of one arboviral genotype with another, however, has not been systematically examined. Accordingly, we will test the hypothesis that dominance of one WNV genotype may result from selective advantages of this genotype in the mosquito and/or avian host. Specifically, proposed studies will focus on whether this dominance is achieved through differential potential for genetically defined WNV strains to (a) be transmitted vertically and subsequently perorally by mosquitoes, (b) infect, produce viremia and viral shedding in ecologically relevant vertebrate hosts. Further, we propose experiments that will determine whether these phenotypic differences are associated with differences at the cellular level in viral replication events. Finally, we will determine the point(s) in the WNV transmission cycle that are likely to have been responsible for the observed extinction of one viral genotype as it has been displaced with another in the U.S. Interactions of an arbovirus with both vertebrate and invertebrate hosts impact the intensity of virus transmission and thereby alter the rate of enzootic amplification, genetic stability of the virus, and subsequent viral fitness. Results from these studies will have direct implications on public health by increasing our understanding of the selective processes that shape invasive vector-borne virus populations using WNV as a model system for a vector-borne disease agent introduced into a naive environment.