Quasispecies dynamics in arbovirus persistence emergence and fitness

虫媒病毒持久性出现和适应性的准种动态

• 批准号: 8901902
• 负责人: Gregory David Ebel
• 金额: $ 37.13万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-15 至 2017-02-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8901902
• 关键词: Aedes; Alphavirus; American; Arboviruses; Birds; Characteristics; Chikungunya virus; Competence; Crows; Culex (Genus); Culex pipiens; Culicidae; Data; Disease; Disease Outbreaks; Ecology; Environment; Evolution; Flaviviridae; Flavivirus; Frequencies; Funding; Genetic; Genetic Variation; Genotype; Health; Horizontal Disease Transmission; Housing; Individual; Infection; Laboratories; Laboratory Study; Lead; Link; Literature; Maintenance; Measures; Mediating; Methods; Minor; Modeling; Mus; Nature; Nucleotides; Observational Study; Pathogenesis; Pathway interactions; Population; Population Dynamics; Population Genetics; Population Heterogeneity; Predisposition; Process; Public Health; Publications; RNA Interference; RNA Sequences; RNA Viruses; Research; Robin bird; Shapes; Site; Small RNA; Sparrows; Testing; Time; Togaviridae; Variant; Vertebrates; Viral; Virus; Virus Diseases; West Nile virus; Work; deep sequencing; field study; fitness; in vivo; innovation; mortality; mutant; novel; novel virus; response; transcriptome sequencing; transmission process; vector; vector mosquito; viral RNA; virus genetics; virus host interaction; wild bird

DESCRIPTION (provided by applicant): Local, site-specific characteristics largely control the transmission dynamics of arthropod-borne viruses (arboviruses). Arboviruses, in turn, adapt to local conditions, maximizing their potential to perpetuate and emerge as health threats. The adaptive potential of arboviruses is driven by error-prone replication, which creates a genetically diverse pool of competing virus genotypes within each host. This application examines the influence of three important characteristics of any given transmission focus on viral genetic diversity; and how genetic diversity influences host-virus interactions. Our previous research has allowed us to make very clear predictions about each of the three examined characteristics. The frequency of contact between mosquitoes and vertebrates varies in time and space. Aim 1 will determine how the frequency of this contact influences the genetic diversity of West Nile virus (WNV) using a laboratory model transmission cycle. We predict that shorter incubation in mosquitoes allows maintenance of viral genetic diversity and high fitness. A second critical characteristic of a transmission focus is the mosquito species involved in virus transmission. Aim 2 will therefore assess how important vector mosquitoes differ in their ability to respond to WNV infection through RNA interference (RNAi) and thus drive virus diversification. Field-collected and colonized Culex (main) and Aedes (secondary) mosquitoes will be assessed. We predict that significant variation in RNAi activation will be detected within and between mosquito species, and that this variation will be associated with virus genetic diversity and altered vector competence. A third critical characteristic of a WNV transmission focus is the bird species involved in virus amplification. Aim 3, accordingly, will evaluate how crows, sparrows and robins shape WNV populations. Virus will be passed in each of these birds and genetic diversity and fitness assessed. We will also use these birds to measure the replicative fitness of different existing WNV strains and populations. We predict that wild birds exert strong purifying selection on WNV populations and that genetic diversity of the virus contributes little to its fitness in birs, but that bird infection may select for novel WNV genotypes. The significance of this work is that it will provide novel data the mechanisms that underpin the emergence of RNA viruses as health threats. The proposed research is conceptually innovative because it links the ecology of WNV transmission foci with virus adaptive plasticity. It is technically innovative because it uses uniqe methods for measuring virus fitness among relevant hosts in vivo and through its use of deep sequencing. Ultimately we seek to define the conditions that favor the emergence of novel virus genotypes.

描述（由申请人提供）：本地，特定于现场的特征在很大程度上控制了节肢动物传播病毒（arboviruses）的传播动力学。反过来，Arbovirus会适应当地条件，从而最大程度地将其延续为健康威胁的潜力。 arbovirus的自适应潜力是由易于错误的复制驱动的，该复制在遗传上创造了 每个宿主内的竞争病毒基因型的各种池。该应用研究了任何给定传播的三个重要特征的影响，侧重于病毒遗传多样性。以及遗传多样性如何影响宿主病毒相互作用。我们以前的研究使我们能够对三个经过检查的特征中的每个特征做出非常清楚的预测。蚊子和脊椎动物之间的接触频率在时间和空间上有所不同。 AIM 1将通过实验室模型传输周期来确定这种接触的频率如何影响西尼罗河病毒（WNV）的遗传多样性。我们预测，蚊子中的较短孵育可以维持病毒遗传多样性和高适应性。传播重点的第二个关键特征是参与病毒传播的蚊子物种。因此，AIM 2将评估媒介蚊子通过RNA干扰（RNAI）对WNV感染的反应能力有何不同，从而驱动病毒多样化。将评估田间收​​集和定植的库尔克斯（Main）和埃德（Main）（二级）蚊子。我们预测，在蚊子物种之间和之间，将检测到RNAi激活的显着差异，并且这种变异将与病毒遗传多样性和改变相关。 权限。 WNV传播焦点的第三个关键特征是参与病毒扩增的鸟类。 AIM 3因此，将评估乌鸦，麻雀和知更鸟如何塑造WNV种群。这些鸟类将通过这些鸟类以及评估的遗传多样性和适应性通过病毒。我们还将使用这些鸟来测量不同现有WNV菌株和种群的复制适应性。我们预测野生鸟对WNV种群施加了强烈的纯化选择，并且该病毒的遗传多样性对其在BIRS中的适应性不大，但是该鸟类感染可能会选择新型的WNV基因型。这项工作的意义在于，它将提供新的数据，即作为健康威胁的RNA病毒出现的机制。拟议的研究在概念上是创新的，因为它将WNV传播灶的生态学与病毒自适应可塑性联系起来。它在技术上具有创新性，因为它使用Uniqe方法来测量体内相关宿主之间的病毒适应性，并通过使用深度测序。最终，我们试图定义有利于新病毒基因型出现的条件。