Mechanisms of WNV Selection and Strain Displacement

WNV 选择和应变位移的机制

• 批准号: 7493503
• 负责人: Laura D Kramer
• 金额: $ 20万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2009-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7493503
• 关键词: Mechanisms; WNV; Selection; Strain; Displacement

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 na'fve 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.

提出研究旨在解决计划公告中的目标3 PA04052。引入 在北美相对良好的时间和地点，单个WNV菌株提供了独特的 前瞻性研究节肢动物传播的RNA病毒的演变，因为它适应了Na'fve 生态利基。虽然美洲的WNV仍然是一个相对均匀的病毒人群 与引入的基因型不同的基因型已经出现，在北部的大部分地区占主导地位 自2002年以来，美国已经在纽约取代了以前现有的基因型。初步的 研究表明，这种新基因型的优势可以通过病毒之间的相互作用来促进 和蚊子主持人。可能导致一个生物学机制的范围 然而，尚未系统地检查Arbovirus基因型。此外，范围 WNV和其他节肢动物传播病毒的遗传变异可能伴随的表型表达 没有很好的特征，难以预测。因此，我们将检验以下假设 一种WNV基因型可能是由于该基因型在蚊子和/或禽宿主中的选择性优势而产生的。 具体而言，拟议的研究将集中于是否通过差异潜力实现这种优势 对于（a）产生脊椎动物病毒血症的遗传定义的WNV菌株，（b）通过口头传播 蚊子和（c）从感染的雌性蚊子垂直传播到其后代。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WNV传输周期中的点 可能是导致观察到的一种WNV基因型与另一种WNV基因型的位移。 这些研究的结果将极大地增加我们对选择性过程的理解 塑造天然arbovirus人群。