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) 是一种由蚊子传播的病原体，会导致发热性疾病，有时会导致 致命性脑炎，是 20 世纪 70 年代美国传染性脑炎的主要原因。 2015 年至 2021 年，SLEV 在加利福尼亚州重新出现并重新建立，并导致 亚利桑那州菲尼克斯附近的 SLEV 疫情再次爆发，其特点是人类病例不断增加，且呈阳性。 每年有更多县出现蚊子池，其中包括西尼罗河病毒同时活动的地区 (WNV)，一种相关的黄病毒，于 2003 年入侵加利福尼亚州，与鸟类和库蚊共享宿主 我们团队的基因追踪显示，SLEV 在西方重新出现（“当代”）。 美国在基因上与 2003 年之前（“历史”）的 SLEV 不同，并且它可能起源于南美洲。 然而，除了这些研究之外，SLEV 重新出现的驱动因素，包括进入西尼罗河病毒流行地区， 禽类宿主感染的增加促进了西尼罗河病毒在美国的传播。 我们认为类似的适应性增益可能使 SLEV 重新出现。 该项目的目标是评估增强型车辆在多大程度上促进 SLEV 重新出现 蚊子和鸟类细胞以及蚊媒的传染性和传播性较高的 SLEV 活性。 不同的区域可以通过 3 个主要库蚊媒介（pipiens、 tarsalis 和 quinquefasciatus）有利于全州不同的环境。 自 2015 年以来在美国西部的重新出现是通过引入基因型的增强适应性来介导的 细胞和载体，地理定位受 3 个主要载体相对能力的影响 库蚊种类可以通过使用载体比较 SLEV 菌株来进行实验评估。 项目假设将在 2 个项目中进行测试 目标： 1) 确定 当代与历史 SLEV 在库蚊媒介中的传播能力，以及 2) 比较相对值 当代与历史 SLEV 在鸟类和蚊子细胞和载体中的适应性。 重要的是，它将提供一个独特的机会来比较顺序入侵中涉及的病毒因素 以及 2 种库蚊传播的黄病毒的传播，了解共循环动力学可以应用于其他 通过定义库蚊媒介物种在 SLEV 传播中的作用，该项目将 确定传染性和传播性的增强是否是增强重新出现和传播的因素。 为了减少疾病，媒介控制区可以分配资源用于库蚊媒介的空间定位 表现出高 SLEV 能力的物种。