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 建议针对PA-04-119生物防御和新发传染病进行研究 疾病研究机会。西尼罗河病毒是NIAID B类优先病原体。这个 在相对较好的时间和地点引入单一的西尼罗河病毒株 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，因为它适应天然的生态环境。而西尼罗河畔 在美洲，仍然是一个相对同质的病毒群体，单一的基因 这与引进的基因不同，它已经成为整个北方的主导 美国，自2002年以来，已经取代了美国以前存在的基因型 各州。初步研究表明，这种新基因的优势可能是 通过病毒和蚊子宿主之间的相互作用以及通过 与自然鸟类宿主的相互作用。可能导致的一系列生物机制 然而，对于一种虫媒病毒基因与另一种虫媒病毒基因的置换， 系统地研究了。因此，我们将检验一个人的统治地位的假设 西尼罗河病毒的基因分型可能源于该基因在蚊子中的选择优势。 和/或禽类宿主。具体地说，拟议中的研究将集中在这种优势是否 通过基因定义的西尼罗河病毒株的差异潜力实现(A)BE 由蚊子垂直传播，然后经口传播；(B)感染、繁殖 与生态相关的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与 病毒复制事件在细胞水平上的差异。最后，我们将确定 西尼罗河病毒传播周期中可能负责的点(S) 观察到的一种病毒基因的灭绝，因为它与另一种病毒基因发生了置换 美国虫媒病毒与脊椎动物和无脊椎动物宿主的相互作用影响 病毒传播的强度，从而改变地方病的扩大率， 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 对公众健康有直接影响，因为我们增加了对选择性 以西尼罗河病毒为模型塑造侵袭性媒介传播病毒种群的过程 用于将病媒传播的病原体引入幼稚环境的系统。