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
• 负责人: Nisha Duggal
• 金额: $ 20.44万
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10308835
• 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.

项目摘要 西尼罗河病毒（WNV），圣路易斯脑炎病毒（SLEV）和USUTU病毒（USUV）密切相关 蚊子传播的病毒在人类中引起神经脱落性疾病。所有三种病毒都保持在 重叠的鸟/蚊子循环，向人类溢出。 1999年将WNV引入美国 由于鸟类的交叉反应性免疫反应，迅速将先前循环的SLEV移位。但是， SLEV的新型基因型最近在美国出现，在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的SLEV基因型。 USUV最近出现了 在欧洲，至少从非洲引入了三次。我们发现房屋麻雀 （Passer foreflus）和Culex Quinquefasciatus蚊子，具有WNV和SLEV的能力 也容易受到USUV的影响。该项目的长期目标是了解影响新颖的因素 黄病毒的出现是为了预测人类的爆发。这项研究的目标是确定 有能力的北美鸟类和蚊子为USUV，并确定WNV免疫的作用 在SLEV和USUV出现的鸟类中。假设是新型SLEV基因型和USUV具有 由于有能力，建立或有可能在北美建立传输周期 当地的鸟类和蚊子以及鸟类中WNV免疫的逃避，从而导致风险增加 人类的神经侵袭性疾病。两个具体目标将解决这一假设：1）确定北方是否是否 美国的passerines和蚊子有能力为USUV； 2）评估以前的影响 在鸟类中暴露于SLEV和USUV感染中的WNV。在第一个目标中，我们将捕获三种野鸟 确定当地鸟类对USUV的敏感性。我们将量化USUV的感染阈值 通过在受感染的鸟类上喂食蚊子，然后测量传染病，然后在 期望被感染的蚊子。在第二个目标中，WNV预曝光对随后的影响 新型SLEV基因型和USUV的感染将在鸟类中进行评估。接种鸟的血清将是 测试了针对所有三种病毒的体外中和活性，以确定诊断的能力 使用血清学识别黄病毒感染。这里提出的研究是创新的，因为它 研究了一种新型的SLEV基因型和被忽略的USUV，使用一种新型的禽类病毒 实验模型。成功完成拟议的研究后，预期的贡献 工作将是识别USUV储层和矢量物种以及影响Enzootic的因素 SLEV和USUV的传输。预计这项贡献将是重要的，因为了解 新兴黄病毒的传播周期将导致预测人类疾病的能力。