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）是一种蚊子出生的病原体，会引起高温疾病，有时 致命性脑炎，在1970年代是美国传染性脑炎的主要原因。 11-之后 从2015 - 2021年开始，SLEV在加利福尼亚州的活动中缺席，并在CA中重新建立了 亚利桑那州凤凰城附近的爆发。 SLEV的重新出现以增加人类病例和积极为标志 每年更多县的蚊子池，包括西尼罗河病毒同时活动的地区 （WNV），一种相关的黄病毒，在2003年入侵CA，并共享禽类水库和Culex蚊子 带有SLEV的向量。我们的团队的遗传追踪表明，西方的重新出现（“当代”）SLEV 美国在遗传上与2003年前（“历史”）SLEV不同，它可能起源于南美。 但是，除了这些研究之外，SLEV重新出现的驱动因素（包括进入WNV端区）具有 没有被检查。 WNV在美国的传播是通过增强的鸟类水库感染和 向量能力。我们建议类似的健身增长可能使SLEV重新出现。这 该项目的目的是评估通过增强促进SLEV重新出现的程度 蚊子和禽类细胞和蚊子载体的感染性和传播性。较高的SLEV活动 不同区域可以通过3个主要Culex载体的差分矢量能力来解释（pipiens， tarsalis和quinquefasciatus），偏爱全州不同的环境。我们假设SLEV 自2015年以来，美国西部的重新出现是通过引入基因型的增强健身性的介导的 细胞和矢量以及该地理位置的定位受3个主要的相对矢量能力的影响 Culex物种。可以通过使用载体比较SLEV菌株来实验评估病毒适应性 能力和竞争分析。项目假设将在2个项目目标中进行测试：1）确定 当代载体中当代与历史SLEV的传播能力，以及2）比较亲戚 当代与历史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，比较涉及顺序入侵的病毒因素 并扩散2个Culex传播黄病毒，其中理解共循环动力学可以应用于其他 同胞黄病毒。通过定义Culex Vector物种在SLEV传输中扮演的角色，这个项目将 确定增强感染和传播是否是增强重新出现和扩散的因素。 为了减少疾病，媒介控制区可以分配资源以空间靶向Culex Vector 暴露了高SLEV能力的物种。