Transmission dynamics and fitness of reemerging St. Louis encephalitis virus

重新出现的圣路易斯脑炎病毒的传播动力学和适应度

• 批准号: 10645668
• 负责人: Lark L Coffey
• 金额: $ 24万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-03 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645668
• 关键词: Area; Arizona; Biological Assay; Birds; Blood; California; Cell Culture Techniques; Cells; Competence; Complement; County; Culex (Genus); Culex pipiens; Culicidae; Disease; Disease Outbreaks; Dose; Ducks; Embryo; Encephalitis; Environment; Epidemic; Exhibits; Extinction; Fever; Fibroblasts; Flavivirus; Genetic; Genetic study; Genotype; Geography; Goals; Herd Immunity; Human; Immunity; Incubated; Infection; Infectious Encephalitis; Ingestion; Invaded; Learning; Measures; Mediating; Pattern; Persons; Play; Process; Resource Allocation; Role; Saliva; Sampling; South America; St. Louis Encephalitis Virus; Testing; Time; Tissues; Viral; Virus; Virus Diseases; West Nile virus; enhancing factor; enzootic; fitness; human pathogen; improved; mosquito-borne; mosquito-borne pathogen; novel; novel strategies; transmission process; vector; vector competence; vector control; vector mosquito; viral RNA; viral fitness; viral transmission; virus genetics

St. Louis encephalitis virus (SLEV) is a mosquito borne pathogen that causes febrile illness and sometimes fatal encephalitis and was a leading cause of infectious encephalitis in the US during the 1970s. After an 11- year absence in activity in California, SLEV reemerged and reestablished in CA from 2015-2021, and caused an outbreak in nearby Phoenix, AZ. SLEV reemergence is marked by increasing human cases and positive mosquito pools across more counties each year, including areas with concurrent activity of West Nile virus (WNV), a related flavivirus that invaded CA in 2003 and which shares avian reservoirs and Culex mosquito vectors with SLEV. Genetic tracing by our team showed that reemerging (‘contemporary’) SLEV in the Western US is genetically distinct from pre-2003 (‘historical’) SLEV and that it likely originated in South America. However, other than these studies, drivers of SLEV reemergence, including into WNV-endemic areas, have not been examined. Spread of WNV across the US was facilitated by augmented avian reservoir infection and vector competence. We propose that similar fitness gains may have enabled SLEV reemergence. The objective of this project is to assess the extent by which SLEV reemergence is promoted by augmented infectivity and transmissibility in mosquito and avian cells and mosquito vectors. Higher SLEV activity in different regions may be explained by differential vector competence for 3 primary Culex vectors (pipiens, tarsalis, and quinquefasciatus) that favor different environments across the state. We hypothesize that SLEV reemergence in the Western US since 2015 was mediated by augmented fitness of the introduced genotype in cells and vectors and that geographic localization is influenced by relative vector competence of 3 primary Culex species. Viral fitness can be assessed experimentally by comparing SLEV strains using vector competence and competition assays. The project hypotheses will be tested in 2 project Aims: 1) Determine transmission competence of contemporary versus historical SLEV in Culex vectors, and 2) Compare relative fitness of contemporary versus historical SLEV in avian and mosquito cells and vectors. This project is significant in that it will provide a unique opportunity to compare viral factors involved in the sequential invasion and spread of 2 Culex-borne flaviviruses, where understanding co-circulation dynamics can be applied to other sympatric flaviviruses. By defining the role Culex vector species play in SLEV transmission this project will determine whether augmented infectivity and transmissibility is a factor enhancing reemergence and spread. To reduce disease, vector control districts can allocate resources towards spatial targeting of the Culex vector species that exhibit high SLEV competence.

圣路易斯脑炎病毒（SLEV）是一种蚊子传播的病原体，可引起发热性疾病，有时 致命性脑炎，是20世纪70年代美国传染性脑炎的主要原因。在11- 在加州，SLEV在2015年至2021年期间重新出现并在加州重新建立，并导致 亚利桑那州凤凰城附近爆发了疫情。SLEV重新出现的特点是人类病例增加， 每年有更多的县出现蚊子聚集地，包括同时存在西尼罗河病毒的地区 (WNV)这是一种相关的黄病毒，2003年入侵加利福尼亚州， SLEV的载体。我们团队的基因追踪表明，西方国家重新出现的（“当代”）SLEV 美国与2003年以前（“历史”）的SLEV在基因上不同，它可能起源于南美洲。 然而，除了这些研究，SLEV重新出现的驱动因素，包括进入WNV流行地区， 没有被检查。西尼罗河病毒在美国的传播是由增加的禽类水库感染促进的， 向量能力我们认为，类似的健身增益可能使SLEV重新出现。的 本项目的目的是评估SLEV重新出现的程度， 在蚊子和鸟类细胞以及蚊子载体中的感染性和传播性。SLEV活性更高， 不同的区域可以通过3种主要库蚊载体（尖音库蚊， tarsalis和quinquefasciatus），有利于全州不同的环境。我们假设SLEV 自2015年以来在美国西部的重新出现是由引入的基因型的适应性增强介导的， 细胞和载体，地理定位受3个主要的载体相对能力的影响， 库蚊属。病毒适应性可以通过使用载体比较SLEV毒株来实验性地评估。 能力和竞争测定。项目假设将在2个项目目标中进行测试：1）确定 当代与历史SLEV在库蚊媒介中的传播能力，以及2）比较相对 现代与历史SLEV在鸟类和蚊子细胞和载体中的适应性。这个项目是 重要的是，它将提供一个独特的机会，比较病毒因素参与的顺序入侵 和传播2库克斯传播的黄病毒，其中了解共循环动力学可以应用于其他 同域黄病毒通过确定库蚊媒介物种在SLEV传播中的作用，该项目将 确定增强的传染性和传播性是否是一个因素，提高了重新出现和传播。 为减少疾病，病媒控制区可将资源用于库蚊病媒的空间定位 表现出高SLEV能力的物种。