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
• 负责人: Nisha Duggal
• 金额: $ 22.81万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-21 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10408846
• 关键词: Address; Africa; African; American; Americas; Arboviruses; Area; Arizona; Birds; California; Cells; Chickens; Competence; Culex (Genus); Culex pipiens; Culicidae; Data; Diagnostic; Disease; Disease Outbreaks; Europe; Experimental Models; Exposure to; Finches; Flavivirus; Flavivirus Infections; Future; Genotype; Goals; Human; Immune response; Immunity; In Vitro; Infection; Measures; Modeling; Mosquito-borne infectious disease; North America; Predisposition; Public Health; Reporting; Research; Risk; Role; Saliva; Sentinel; Serology; Sparrows; St. Louis Encephalitis Virus; Therapeutic; Time; Vaccines; Viral; Viral reservoir; Viremia; Virus; Virus Diseases; West Nile virus; Work; Zoonoses; cross reactivity; enzootic; feeding; in vitro testing; in vivo; innovation; mosquito-borne; neglect; neutralizing antibody; novel; programs; response; spillover event; surveillance strategy; transmission process; vector; vector competence; viral transmission; virus genetics; wild bird

Project Summary West Nile virus (WNV), St. Louis encephalitis virus (SLEV), and Usutu virus (USUV) are closely-related mosquito-borne viruses that cause neuroinvasive disease in humans. All three viruses are maintained in overlapping bird/mosquito cycles, with spillover to humans. The introduction of WNV into the U.S. in 1999 quickly displaced the previously-circulating SLEV due to cross-reactive immune responses in birds. However, a novel genotype of SLEV recently emerged in the U.S., causing an outbreak in 2015, and we have found that WNV immune responses in birds do not neutralize the novel SLEV genotype in vitro. USUV recently emerged in Europe, where it has been introduced at least three times from Africa. We have found that House sparrows (Passer domesticus) and Culex quinquefasciatus mosquitoes, which are competent for WNV and SLEV, are also susceptible to USUV. The long-term goal of this project is to understand the factors that influence novel flavivirus emergence in order to predict outbreaks in humans. The objectives of this study are to identify competent North American avian and mosquito species for USUV and to determine the role of WNV immunity in birds on SLEV and USUV emergence. The hypothesis is that the novel SLEV genotype and USUV have established or have the potential to establish transmission cycles in North America due to the competence of local birds and mosquitoes and the evasion of WNV immunity in birds, thus leading to an increased risk of neuroinvasive disease in humans. Two specific aims will address this hypothesis: 1) Determine whether North American passerines and mosquitoes are competent for USUV; and 2) Assess the influence of previous exposure to WNV on SLEV and USUV infection in birds. In the first aim, we will trap three species of wild birds to determine the susceptibility of local birds to USUV. We will quantify the infectious threshold of USUV for bird-to-mosquito transmission by feeding mosquitoes on infected birds and then measure infectious virus in the expectorate of infected mosquitoes. In the second aim, the effect of WNV pre-exposure on subsequent infection by the novel SLEV genotype and USUV will be evaluated in birds. Sera from inoculated birds will be tested for in vitro neutralizing activity against all three viruses to determine the capacity for diagnostically identifying flavivirus infections using serology. The research proposed here is innovative because it investigates a novel SLEV genotype and USUV, which are neglected, emerging viruses, using a novel avian experimental model. Upon successful completion of the proposed research, the anticipated contribution of this work will be the identification of USUV reservoir and vector species and factors that influence enzootic transmission of SLEV and USUV. This contribution is expected to be significant because understanding the transmission cycle of emerging flaviviruses will lead to the ability to predict disease in humans.

项目概要 西尼罗河病毒（WNV）、圣路易斯脑炎病毒（SLEV）和乌苏图病毒（USUV）密切相关 蚊媒病毒，可导致人类神经侵袭性疾病。所有三种病毒均保存在 鸟类/蚊子周期重叠，并蔓延至人类。 1999 年西尼罗河病毒进入美国 由于鸟类的交叉反应性免疫反应，迅速取代了之前流通的 SLEV。然而，一个 最近在美国出现了 SLEV 的新基因型，导致 2015 年爆发，我们发现 鸟类中的 WNV 免疫反应不会在体外中和新型 SLEV 基因型。最近出现的USUV 在欧洲，它已至少三次从非洲引入。我们发现麻雀 (Passer Domesticus) 和 Culex quinquefasciatus 蚊子具有 WNV 和 SLEV 能力， 也容易受到 USUV 的影响。该项目的长期目标是了解影响小说的因素 黄病毒的出现是为了预测人类的爆发。本研究的目的是确定 能够胜任 USUV 的北美鸟类和蚊种，并确定西尼罗河病毒免疫的作用 在鸟类上SLEV和USUV的出现。假设新型 SLEV 基因型和 USUV 具有 由于以下人员的能力，已在北美建立或有可能建立传输周期 当地鸟类和蚊子以及鸟类逃避西尼罗河病毒免疫力，从而导致感染病毒的风险增加 人类神经侵袭性疾病。有两个具体目标将解决这一假设：1）确定 North 是否 美洲雀形目和蚊子都能胜任USUV； 2）评估先前的影响 接触西尼罗河病毒对鸟类 SLEV 和 USUV 感染的影响。在第一个目标中，我们将捕获三种野鸟 以确定当地鸟类对 USUV 的敏感性。我们将量化 USUV 的传染阈值 通过将蚊子喂给受感染的鸟类来进行鸟类到蚊子的传播，然后测量鸟类中的传染性病毒 受感染蚊子的痰液。在第二个目标中，西尼罗河病毒预暴露对后续的影响 新型 SLEV 基因型和 USUV 的感染将在鸟类中进行评估。来自接种疫苗的禽类的血清将被 测试了针对所有三种病毒的体外中和活性，以确定诊断能力 使用血清学鉴定黄病毒感染。这里提出的研究具有创新性，因为它 研究了一种新的 SLEV 基因型和 USUV，它们是被忽视的新兴病毒，使用一种新型禽类 实验模型。成功完成拟议的研究后，该研究的预期贡献 工作将是确定 USUV 储存库和媒介物种以及影响地方性动物流行的因素 SLEV 和 USUV 的传输。预计这一贡献将是重大的，因为了解 新兴黄病毒的传播周期将带来预测人类疾病的能力。

项目成果

North American House Sparrows Are Competent for Usutu Virus Transmission.

• DOI: 10.1128/msphere.00295-22
• 发表时间: 2022-12-21
• 期刊: MSPHERE
• 影响因子: 4.8
• 作者: Kuchinsky, Sarah C.;Marano, Jeffrey;Hawks, Seth A.;Loessberg, Emma;Honaker, Christa F.;Siegel, Paul B.;Lahondere, Chloe;LeRoith, Tanya;Weger-Lucarelli, James;Duggal, Nisha K.
• 通讯作者: Duggal, Nisha K.