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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

基本信息

批准号：
8554357
负责人：
Gregory David Ebel
金额：
$ 35.29万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-15 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8554357
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 transmission process vector vector mosquito viral RNA virus genetics virus host interaction wild bird

项目摘要

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）：局部、位点特异性特征在很大程度上控制了节肢动物传播的病毒（虫媒病毒）的传播动态。反过来，虫媒病毒适应当地条件，最大限度地发挥其持续存在并成为健康威胁的潜力。虫媒病毒的适应潜力是由易出错的复制驱动的，这产生了一种遗传