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.

建议进行研究以解决计划公告PA 04052中的目标3。的引入 在北美相对较好表征的时间和地点的单一西尼罗河病毒株提供了独特的 有机会前瞻性地研究节肢动物传播的RNA病毒的进化，因为它适应了一个天真的 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种群， 与引进的基因型不同的基因型已经出现，在北方大部分地区占主导地位。 自2002年以来，它在很大程度上取代了以前在纽约存在的基因型。初步 研究表明，这种新基因型的优势可能是由病毒之间的相互作用促进的。 和蚊子宿主之间的关系一系列的生物机制，可能会导致一个位移 然而，虫媒病毒基因型与另一种基因型的关系尚未得到系统的研究。此外，范围 表型表达可能伴随着西尼罗河病毒和其他节肢动物传播病毒的遗传变异 没有很好的描述，也很难预测。因此，我们将测试假设， 一种WNV基因型可能是由于该基因型在蚊子和/或禽类宿主中的选择性优势。 具体来说，拟议的研究将集中在是否这种优势是通过差分电位实现的 对于遗传上确定的WNV毒株，（a）产生脊椎动物病毒血症，（B）通过口服传播 （c）由受感染的雌蚊垂直传染给其后代。我们还 提出实验，以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， 很可能是负责观察到的位移一个西尼罗河病毒基因型与另一个。 这些研究的结果将大大增加我们对选择性过程的理解， 塑造自然虫媒病毒种群。