West Nile Virus Genotypic Affect on Host Competence

西尼罗河病毒基因型对宿主能力的影响

• 批准号: 6912886
• 负责人: Aaron Cole Brault
• 金额: $ 20.34万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2007-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6912886
• 关键词: Aedes; Aves; Culicidae; West Nile virus; communicable disease transmission; disease outbreaks; disease reservoirs; disease vectors; ecology; epizootiology; gene mutation; genetic manipulation; genetic strain; genotype; host organism interaction; immunogenetics; natural selections; virus genetics; wild animals

Description (provided by applicant): West Nile virus (WNV) has become the leading cause of arboviral encephalitis in the United States. The most notable epidemiological factors associated with the rapid emergence of WNV have been the development of high viral titers within birds and the wide range of mosquito vectors implicated with transmission. Despite the use of bird mortality as a sentinel for WNV activity, the underlying viral genetic basis for WNV pathogenicity in birds and the role of increased vector competence in the transmission of WNV are poorly understood. Generation of fundamental data on the basis of replication within the WNV avian reservoir and insect vector will fill critical gaps in our knowledge of WNV transmission and aid in the improvement of existing surveillance strategies and predictive emergence models for the prevention of human and veterinary disease. The fact that a single gene alteration can impact on the transmission potential of WNV indicates the strong need for genotypic monitoring and virulence characterization of WNV as it moves into new ecological niches that may select for additional genetic change. Our overall hypothesis that that an invading virus must evolve and alter its virulence to adapt to new ecological niches will be addressed by the following three specific aims: (1) Identify WNV fitness differences between the introduced NY99 genotype and strains isolated from North American birds and mosquitoes since 1999 as well as other WNV strains from Australia, Kenya and South Africa. Highly sensitive viral fitness assays will be employed as a marker for the detection of phenotypic differences in standardized high, medium and low susceptible avian and mosquito hosts using in vivo assays (2) Characterize the specific role of genetic substitutions identified for host adaptation by engineering the genetic changes into an infectious cDNA made from an early WNV isolate following North American introduction (3) Determine if long term persistence in avian or mosquito hosts during the overwintering period results in consistent genetic change that alter viremogenic potential after vernal termination. These data could help explain why WNV epidemics seem most extensive the year following introduction into new geographical areas. Virus isolated from chronically infected birds or passed vertically from infected mosquitoes will be examined for genetic changes associated with the avoidance of the host immune systems that allow for persistence. Completion of these specific aims will provide new insight into the selective mechanisms that modulate viral emergence and specifically delineate Iviral genetic changes associated with avian/mosquito infectivity that have facilitated the transcontinental epidemic of West Nile virus in North America.

描述（由申请人提供）：西尼罗河病毒（WNV）已成为美国砷病毒脑炎的主要原因。与WNV快速出现相关的最显着的流行病学因素是鸟类中高病毒滴度的发展以及与传播有关的广泛蚊子媒介。尽管将鸟类死亡率用作WNV活性的前哨，但对鸟类中WNV致病性的潜在病毒遗传基础以及载体能力提高在WNV传播中的作用知之甚少。基本数据基于WNV禽类储层和昆虫载体内的复制，将填补我们对WNV传播的了解的关键空白，并有助于改善现有的监视策略以及预防人类和兽医疾病的预测出现模型。单个基因改变会影响WNV的传播潜力的事实表明，当WNV进入新的生态壁ches时，对基因型监测和毒力表征的强烈需求，可以选择其他遗传变化。我们的总体假设是，必须通过以下三个具体目的来解决入侵病毒必须发展并改变其毒力以适应新的生态壁ches：（1）确定自1999年以来与北美鸟类和蚊子从北美鸟类和蚊子中脱离的NY99基因型和菌株之间的WNV适应性差异，以及其他WNV。 Highly sensitive viral fitness assays will be employed as a marker for the detection of phenotypic differences in standardized high, medium and low susceptible avian and mosquito hosts using in vivo assays (2) Characterize the specific role of genetic substitutions identified for host adaptation by engineering the genetic changes into an infectious cDNA made from an early WNV isolate following North American introduction (3) Determine if long term persistence in avian or蚊子在越冬期间宿主会导致遗传变化一致，从而改变了春季终止后的病毒性潜力。这些数据可以帮助解释为什么WNV流行病在引入新的地理区域之后的一年似乎最广泛。将检查从长期感染的鸟类中分离出来的病毒或从感染蚊子垂直传播的病毒，以了解与避免允许持久性的宿主免疫系统相关的遗传变化。这些特定目的的完成将为选择性机制提供新的见解，这些机制调节了与艾鸟/蚊子感染性相关的象牙遗传变化，这些变化促进了北美西尼罗河病毒的跨大陆流行病。