Mechanisms of WNV Selection and Strain Displacement

描述（由申请人提供）：拟开展研究，以解决项目公告PA 04052中的目标3。在北美相对较好的时间和地点引入单一WNV毒株提供了一个独特的机会，可以前瞻性地研究节肢动物传播的RNA病毒的进化，因为它适应了一个幼稚的生态位。虽然西尼罗河病毒在美洲仍然是一个相对同质的病毒群体，但已经出现了一个与引入的基因型不同的单一基因型，在北美大部分地区占主导地位，自2002年以来，在纽约已经在很大程度上取代了以前存在的基因型。初步研究表明，这种新基因型的优势可能是由病毒和蚊子宿主之间的相互作用促进的。然而，可能导致一种虫媒病毒基因型与另一种虫媒病毒基因型置换的生物学机制的范围尚未得到系统的研究。此外，表型表达的范围，可能伴随着遗传变异的西尼罗河病毒和其他节肢动物传播的病毒没有得到很好的表征，难以预测。因此，我们将测试的假设，优势的一个西尼罗河病毒基因型可能会导致这种基因型在蚊子和/或鸟类宿主的选择优势。 具体而言，拟议的研究将集中在这种优势是否是通过遗传定义的西尼罗河病毒株的差异潜力实现的（a）产生脊椎动物病毒血症，（B）由蚊子经口传播，（c）从受感染的雌性蚊子垂直传播给它们的后代。此外，我们提出的实验，将确定这些表型差异是否与相对病毒适应性的差异。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西尼罗河病毒基因型与另一种基因型发生位移的点。这些研究的结果将大大增加我们对自然虫媒病毒种群形成的选择过程的理解。

Description (provided by applicant): Research is proposed to address Objective 3 in Program Announcement PA04052. 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 naive ecological niche. While WNV in the Americas remains a relatively homogeneous virus population, a single genotype that differs from the introduced genotype has arisen, become dominant throughout much of North America, and since 2002 has largely displaced previously existing genotypes in New York. Preliminary studies suggest that the dominance of this new genotype may be facilitated by interactions between the virus and the mosquito host. The range of biological mechanisms that may lead to the displacement of one arbovirus genotype with another, however, have not been systematically examined. Furthermore, the range of phenotypic expression that may accompany genetic variation in WNV and other arthropod-borne viruses is not well characterized and difficult to predict. 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) produce vertebrate viremia, (b) be transmitted orally by mosquitoes, and (c) be transmitted vertically from infected female mosquitoes to their offspring. Further, we propose experiments that will determine whether these phenotypic differences are associated with differences in relative viral fitness. Finally, we will determine the point(s) in the WNV transmission cycle that are likely to have been responsible for the observed displacement of one WNV genotype with another. Results from these studies will dramatically increase our understanding of the selective processes that shape natural arbovirus populations.