Hologenomic basis of WNV vector competence in Culex tarsalis

了解病原体在媒介人群中传播的影响因素对于理解 疾病发病率的动态，新病原体引入的风险评估战略的发展和 开发可用于有效针对控制努力的传播生物标记物。虽然很新奇 寨卡病毒等病原体受到媒体过度关注，B类优先病原体西尼罗河 西尼罗河病毒(WNV)是美国传播最广泛的本地蚊媒病原体。因为它的 1999年，西尼罗河病毒在美国完全传播，确诊人超过50,000人 病例和2,000多人死亡。最有效的实验室媒介是塔氏库蚊，已被确认为 在美国西部是一个非常重要的媒介。我们最近的研究表明， Cx的遗传结构。Tarsalis和西尼罗河病毒在美国西部的入侵模式； 首次研究直接利用蚊子种群遗传学来揭示它们在病原体入侵中的作用。 传统上，媒介能力的差异被归因于蚊子之间的遗传差异。 品系或个体。然而，没有任何有机体是孤立存在的；有机体是一个由 宿主及其相关微生物(细菌、真菌和病毒)，它们共同构成全菌体。 影响病原菌入侵的蚊虫全生体因子目前知之甚少。在这 建议，我们将描绘全息组(蚊子及其相关微生物的遗传学) 西尼罗病毒在CX田间群体中表型变异的因素。塔沙利酒。我们的总体假设是 蚊子全息组的这种变异决定了西尼罗河病毒感染、传播和/或 在实地传播。这一假设将在以下具体目标下进行研究：(1)划定 CX的精细尺度景观遗传学研究。美国的Tarsalis；(2)确定 CX.沙门氏菌微生物群与西尼罗河病毒在CX田间种群的感染、传播和传播 Tarsalis；以及(3)使用复制的混合全基因组关联研究(PoolGwas)来识别基因组座位 与西尼罗河病毒的感染、传播和在CX现场人群中的传播有关。塔沙利酒。 影响病原菌载体能力的全息基因座鉴定及相关遗传研究 种群之间的差异对于理解病原体传播和疾病的模式至关重要 疫情爆发。这项工作对生物恐怖主义问题特别重要，因为它将提供概念性的 洞察自然人群中的内在媒介全息因子如何影响疟疾的流行病学 被释放的B类特工。

Knowledge of the factors influencing pathogen spread in vector populations is critical for understanding dynamics of disease incidence, development of risk assessment strategies for novel pathogen introductions and development of transmission biomarkers that can be used to efficiently target control efforts. Although novel pathogens such as Zika virus receive inordinate media attention, the Category B Priority Pathogen West Nile Virus (WNV) is the most widespread locally transmitted mosquito-borne pathogen in the USA. Since its introduction in 1999, WNV spread completely across the United States with over 50,000 confirmed human cases and over 2,000 deaths. The most efficient laboratory vector is Culex tarsalis, which has been identified as a very important vector in the western United States. Our recent work showed strong correlation between the genetic structure of Cx. tarsalis and the invasion pattern of WNV across the western United States; one of the first studies to directly use mosquito population genetics to implicate their role in pathogen invasion. Traditionally, variation in vector competence has been attributed to genetic differences between mosquito strains or individuals. However, no organism exists in isolation; organisms are a community consisting of the host and its associated microorganisms (bacteria, fungi and viruses) that, collectively, make up the holobiome. Little is known about the mosquito holobiome factors influencing pathogen invasion in the field. In this proposal, we will delineate the hologenomic (genetics of the mosquito and its associated microorganism) factors underlying WNV phenotypic variation across field populations of Cx. tarsalis. Our overall hypothesis is that variation in the mosquito hologenome determines variation in WNV infection, transmission and/or dissemination in the field. This hypothesis will be investigated in the following Specific Aims: (1) Delineate fine-scale landscape genetics of Cx. tarsalis in the United States; (2) Determine the relationship between the Cx. tarsalis microbiome and WNV infection, dissemination and transmission in field populations of Cx. tarsalis; and (3) Use a replicated pooled genome-wide association study (PoolGWAS) to identify genomic loci associated with WNV infection, dissemination and transmission in field populations of Cx. tarsalis. Identification of hologenomic loci affecting pathogen vector competence and studies of correlated genetic variation between populations are critical for understanding patterns of pathogen transmission and disease outbreaks. This work has particular importance for bioterrorism issues because it will provide conceptual insight into how intrinsic vector hologenomic factors in natural populations affect the epidemiology of a released Category B agent.