Transmission dynamics and fitness of reemerging St. Louis encephalitis virus

圣路易斯脑炎病毒(SLEV)是一种蚊子传播的病原体，会引起发烧疾病，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。在一场11- 加州活动缺席一年，2015-2021年，SLEV在加利福尼亚州重新出现并重新建立，并导致 亚利桑那州凤凰城附近爆发疫情。SLEV卷土重来的特点是人类病例和阳性病例增加。 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，于2003年入侵CA，与禽类水库和库蚊共享 带有SLEV的矢量。我们团队的基因追踪显示，在西方重新出现的(当代的)SLEV 美国与2003年前(历史性的)SLEV在基因上是不同的，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，已经 没有经过检查。西尼罗河病毒在美国的传播是由扩大的禽类水库感染和 向量能力。我们认为，类似的适应性增强可能使SLEV卷土重来。这个 该项目的目标是评估SLEV在多大程度上被增强 在蚊子、禽类细胞和蚊媒中的传染性和传播性。更高的SLEV活动在 不同的区域可以用3个主要的库蚊媒介(库蚊， Tarsalis和Ququiefasciatus)，它们适合全州不同的环境。我们假设SLEV 自2015年以来美国西部的重新出现是由引入的基因型的增强适合度介导的 细胞和载体，地理定位受3个主要物种的相对载体能力的影响 库蚊属。病毒适合性可以通过使用载体比较SLEV毒株来进行实验评估 能力和竞争分析。项目假设将在两个项目目标中进行检验：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 当代与历史上的SLEV在鸟类、蚊子细胞和媒介中的适合性。这个项目是 重要的是，它将提供一个独特的机会来比较参与顺序入侵的病毒因素 以及2种库仑传播黄病毒的传播，在这些情况下，对共循环动力学的了解可以应用于其他 同宗的黄病毒。通过定义库蚊媒介物种在SLEV传播中所起的作用，该项目将 确定增加的传染性和传播性是否是促进复发和传播的因素。 为了减少疾病，病媒控制地区可以分配资源用于库蚊病媒的空间靶向 表现出高SLEV能力的物种。

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.