Evolution and pathogenesis of Usutu virus, an emerging arbovirus
一种新兴虫媒病毒乌苏图病毒的进化和发病机制
基本信息
- 批准号:10471848
- 负责人:
- 金额:$ 19.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-19 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAfricaAfricanAmericasAntibodiesArbovirusesAreaAttenuatedAustraliaBlood CirculationCellsChimera organismDNA Sequence AlterationDataDengue VirusDiseaseDoseEncephalitisEpidemicEuropeEuropeanEvolutionFlavivirusFutureGenesGeneticGenetic CrossesGenetic DeterminismGoalsHumanImmuneImmune responseImmunoglobulin GImmunoglobulinsImmunologic FactorsIn VitroInfectionKunjin virusLeadMembraneMeningitisModelingMosquito-borne infectious diseaseMusMutationPathogenesisPathogenicityPoint MutationPrevention strategyPublic HealthResearchResearch PersonnelRiskRoleSerumSystemTestingTherapeuticTimeVaccinesViralViral PathogenesisViremiaVirulenceVirusVirus DiseasesWest Nile virusWild Type MouseWorkZoonosesburden of illnesscross reactivityhuman diseasein vivoinnovationmathematical modelmigratory birdmortalitymosquito-bornemouse modelneglectnovelpredictive modelingpreventprogramsreverse geneticstool developmenttransmission processvaccine developmentvectorvirus genetics
项目摘要
Project Summary
West Nile virus (WNV) and Usutu virus (USUV) are closely-related mosquito-borne viruses that cause
neuroinvasive disease in humans. WNV emerged from African and Europe into the U.S. in 1999, and it is now
the most common mosquito-borne disease in the continental U.S.; however, no vaccines or therapeutics are
available. USUV is emerging in Europe, where it has been introduced at least three times from Africa by
migratory birds, and human disease cases are increasing. The viral factors that lead to increases in flavivirus
pathogenesis include naturally-occurring viral genetic mutations and cross-reactive antibodies from co-
circulating heterologous flaviviruses. We have found that African and European strains of USUV differ
drastically in the level of disease generated in a wild-type mouse model, with differences in viremia of up to
100-fold between USUV strains. We have also found that human WNV convalescent sera partially cross-
neutralizes USUV in vitro. The long-term goal of this project is to understand the effect of viral evolution and
antibody cross-reactivity on flavivirus emergence and disease. The objectives of this study are to identify the
genetic mutations in USUV that dictate differences in pathogenesis and to determine whether WNV cross-
reactive antibodies alter USUV disease. The hypothesis is that viral mutations acquired during emergence
increase USUV pathogenesis and that heterologous WNV antibodies decrease USUV pathogenesis. Two
specific aims will address this hypothesis: 1) Identify viral genetic determinants of USUV disease; and 2)
Determine the impact of WNV antibodies on USUV disease. In the first aim, a reverse genetics system that we
recently developed will be used to identify mutations in USUV that alter viremia and disease in mice. In the
second aim, the effect of IgG purified from human WNV convalescent sera on USUV disease will be evaluated
in vivo. The research proposed here is innovative because it investigates significant differences in
pathogenesis caused by contemporary strains of an emerging, neglected virus using a novel reverse genetics
system. Upon successful completion of the proposed research, the anticipated contribution of this work will be
the identification of viral factors that affect USUV pathogenesis and host immune correlates of USUV disease.
This contribution is expected to be significant because it will lead to the ability to develop therapeutics and
vaccines to reduce flavivirus transmission and disease.
项目概要
西尼罗河病毒(WNV)和乌苏图病毒(USUV)是密切相关的蚊媒病毒,可引起
人类神经侵袭性疾病。西尼罗河病毒于 1999 年从非洲和欧洲进入美国,现在已
美国大陆最常见的蚊媒疾病;然而,目前尚无疫苗或治疗方法
可用的。 USUV 正在欧洲兴起,并已从非洲引进至少 3 次
候鸟和人类疾病病例正在增加。导致黄病毒增加的病毒因素
发病机制包括自然发生的病毒基因突变和来自共同的交叉反应抗体
循环的异源黄病毒。我们发现非洲和欧洲的 USUV 品种有所不同
野生型小鼠模型中产生的疾病水平显着增加,病毒血症的差异高达
USUV 品系之间相差 100 倍。我们还发现人类西尼罗河病毒恢复期血清部分交叉
体外中和 USUV。该项目的长期目标是了解病毒进化的影响和
抗体交叉反应对黄病毒的出现和疾病。本研究的目的是确定
USUV 中的基因突变决定了发病机制的差异,并确定 WNV 是否交叉
反应性抗体改变 USUV 疾病。假设是病毒在出现期间获得突变
增加 USUV 发病机制,异源 WNV 抗体减少 USUV 发病机制。二
具体目标将解决这一假设:1)确定 USUV 疾病的病毒遗传决定因素;和 2)
确定 WNV 抗体对 USUV 疾病的影响。第一个目标是建立一个反向遗传学系统
最近开发的技术将用于识别 USUV 中改变小鼠病毒血症和疾病的突变。在
第二个目标,将评估从人WNV恢复期血清中纯化的IgG对USUV疾病的作用
体内。这里提出的研究具有创新性,因为它调查了
使用新型反向遗传学研究由一种新兴的、被忽视的病毒的当代菌株引起的发病机制
系统。成功完成拟议的研究后,这项工作的预期贡献将是
确定影响 USUV 发病机制的病毒因素以及 USUV 疾病的宿主免疫相关因素。
预计这一贡献将是重大的,因为它将带来开发治疗方法和
减少黄病毒传播和疾病的疫苗。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
West Nile Virus Vaccination Protects against Usutu Virus Disease in Mice.
- DOI:10.3390/v13122352
- 发表时间:2021-11-23
- 期刊:
- 影响因子:0
- 作者:Salgado R;Hawks SA;Frere F;Vázquez A;Huang CY;Duggal NK
- 通讯作者:Duggal NK
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Nisha Duggal其他文献
Nisha Duggal的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Nisha Duggal', 18)}}的其他基金
Evolution and pathogenesis of Usutu virus, an emerging arbovirus
一种新兴虫媒病毒乌苏图病毒的进化和发病机制
- 批准号:
10218381 - 财政年份:2021
- 资助金额:
$ 19.12万 - 项目类别:
Determinants of Usutu virus bird-to-mosquito transmission
乌苏图病毒鸟传蚊的决定因素
- 批准号:
10308835 - 财政年份:2021
- 资助金额:
$ 19.12万 - 项目类别:
Determinants of Usutu virus bird-to-mosquito transmission
乌苏图病毒鸟传蚊的决定因素
- 批准号:
10408846 - 财政年份:2021
- 资助金额:
$ 19.12万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 19.12万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 19.12万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 19.12万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 19.12万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 19.12万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 19.12万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 19.12万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 19.12万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 19.12万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 19.12万 - 项目类别:
Studentship