Mechanisms of West Nile virus selection and strain displacement

西尼罗河病毒选择和毒株置换的机制

• 批准号: 7689572
• 负责人: Laura D Kramer
• 金额: $ 39.74万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-25 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7689572
• 关键词: Address; Africa; American; Americas; Arboviruses; Area; Arthropods; Australia; Biological; Biological Assay; Biological Models; Birds; Canada; Caribbean natives; Caribbean region; Categories; Central America; Columbidae; Competence; Culex (Genus); Culex pipiens; Culicidae; Data; Environment; Epidemic; Epithelial Cells; Europe; Event; Evolution; Extinction (Psychology); Female; Fibrinogen; Flavivirus; Generations; Genetic; Genotype; Goals; Housing; Infection; Infectious Diseases Research; Invasive; Kinetics; Laboratories; Lead; Mexico; Midgut; Modeling; Monitor; National Institute of Allergy and Infectious Disease; New York; New York City; North America; Outcome; Population; Process; Public Health; Publishing; RNA Viruses; Range; Rate; Relative (related person); Research; Research Project Summaries; Rest; Robin bird; Rock Pigeons; Role; Russia; Shapes; South America; Sparrows; System; Testing; Thinking; Time; Tissues; United States; Variant; Vector-transmitted infectious disease; Vertical Disease Transmission; Viral; Viremia; Virus; Virus Shedding; West Nile virus; biodefense; comparative; enzootic; epizootic; feeding; fitness; in vitro Assay; in vivo; invertebrate host; pathogen; research study; transmission process; vector; vector mosquito

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.

项目摘要 提出了研究以解决PA-04-119生物探讨和新兴的感染力 疾病研究机会。 WNV是B类优先病原体。这 在相对良好的时间和位置中引入单个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病毒适应了na¿veve ve ve生态位。 wnv 在美洲仍然是一个相对均匀的病毒群体，一种单一的基因型 与引入的基因型不同，这在整个北部已经占主导地位 自2002年以来，美国已经流离了以前现有的基因型 国家。初步研究表明，这种新基因型的优势可能是 病毒与蚊子宿主之间的相互作用以及由 与天然禽宿主的互动。可能导致的生物机制范围 然而，一种与另一种arboviral基因型的位移还没有 系统检查。彼此之间，我们将检验一个假设，即 WNV基因型可能是由于该基因型在蚊子中的选择性优势而产生的 和/或禽类主持人。具体而言，拟议的研究将集中于这种主导地位是否是 通过遗传定义的WNV菌株的不同潜力来实现（a） 被蚊子垂直传播，随后被蚊子（b）感染，产生 生态相关脊椎动物宿主中的病毒血症和病毒脱落。此外，我们建议 将确定这些表型差异是否相关的实验 病毒复制事件中的细胞水平差异。最后，我们将确定 WNV传输周期中的点可能是负责的 观察到的一种病毒基因型的延伸，因为它已在另一个病毒基因型中取代 美国与脊椎动物和无脊椎动物宿主的美国互动 病毒传播的强度，从而改变enzootic扩增的速率， 病毒的遗传稳定性以及随后的病毒适应性。这些研究的结果将 通过增加我们对选择性的理解，对公共卫生产生直接影响 使用WNV作为模型来塑造侵入性矢量传播病毒群体的过程 媒介疾病剂的系统引入了天真的环境。