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.

计划公告PA04052中提出了针对目标3的研究。引入一种 单一的西尼罗河病毒毒株在北美相对较好的时间和地点提供了独特的 有机会前瞻性地研究节肢动物传播的RNA病毒在适应天然鸟类时的进化 生态位。虽然美洲的西尼罗河病毒仍然是一个相对同质的病毒种群，但单个 与引进的基因不同的基因已经出现，并在北方大部分地区占据主导地位 自2002年以来，在很大程度上取代了纽约以前存在的基因类型。初步 研究表明，病毒之间的相互作用可能促进了这种新基因的显性。 和蚊子宿主。一种可能导致一个人移位的生物机制 然而，虫媒病毒与另一种虫媒病毒的基因型还没有得到系统的检查。此外，范围 可能伴随西尼罗河病毒和其他节肢动物传播病毒遗传变异的表型表达 不是很好的特征，很难预测。因此，我们将检验以下假设： 一种西尼罗河病毒基因可能源于该基因在蚊子和/或禽类宿主中的选择优势。 具体地说，拟议的研究将集中在这种优势是否通过差分势来实现。 对于基因定义的西尼罗河病毒株，(A)产生脊椎动物病毒血症，(B)通过口腔传播 以及(C)从受感染的雌性蚊子向其后代垂直传播。此外，我们 提出实验，以确定这些表型差异是否与 相对病毒适合度的差异。最后，我们将确定西尼罗河病毒传播周期中的一个点(S)， 很可能是导致观察到的一种西尼罗河病毒基因与另一种基因发生移位的原因。 这些研究的结果将极大地增加我们对选择性过程的理解 塑造自然虫媒病毒种群。