Hologenomic basis of WNV vector competence in Culex tarsalis

跗库蚊中西尼罗河病毒载体能力的全基因组基础

• 批准号: 10023155
• 负责人: Jason L Rasgon
• 金额: $ 55.96万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-23 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10023155
• 关键词: Address; Affect; Attention; Bacteria; Biological Markers; Bioterrorism; Categories; Category B pathogen; Cessation of life; Cluster Analysis; Communities; Correlation Studies; Cost Effectiveness Analysis; Culex (Genus); Culicidae; Data; Development; Disease; Disease Outbreaks; Effectiveness; Epidemiology; Event; Gene Frequency; Genes; Genetic; Genetic Population Study; Genetic Recombination; Genetic Structures; Genetic Variation; Genotype; Human; Incidence; Individual; Infection; Insecta; Knowledge; Laboratories; Maps; Microbe; Microsatellite Repeats; Organism; Pattern; Phenotype; Population; Population Genetics; Population Sizes; Process; Quantitative Trait Loci; Research; Resolution; Risk Assessment; Role; Sampling; Statistical Methods; Surveys; System; Technology; Time; United States; Variant; Virus; West Nile viral infection; West Nile virus; Work; Zika Virus; cost; disorder control; experimental study; fungus; genome wide association study; genome-wide; genomic locus; in vivo; insight; interest; microbial; microbiome; microbiome components; microorganism; migration; mosquito-borne pathogen; novel; novel strategies; pathogen; specific biomarkers; statistics; transmission process; vector; vector competence; vector mosquito; viral resistance

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.

了解影响载体种群病原体扩散的因素对于理解至关重要 疾病发病率的动态，开发新的病原体引入的风险评估策略和 开发可用于有效针对控制工作的生物标志物。虽然是新颖的 寨卡病毒等病原体受到过分关注，B类优先级病原体西尼罗河病原体 病毒（WNV）是美国最广泛的局部传播蚊子传播的病原体。自从它 介绍在1999年，WNV在全美国蔓延，有超过50,000人确认的人类 病例和2,000多人死亡。最有效的实验室向量是Culex Tarsalis，已被确定为 美国西部非常重要的向量。我们最近的工作显示 CX的遗传结构。塔萨里斯（Tarsalis）和美国西部WNV的入侵模式；中的一个 首先使用蚊子种群遗传学的研究暗示了它们在病原体侵袭中的作用。 传统上，向量能力的变化归因于蚊子之间的遗传差异 菌株或个人。但是，没有生物存在孤立的生物。有机体是一个由 宿主及其相关的微生物（细菌，真菌和病毒）综合构成了整体。 关于影响该田间病原体侵袭的蚊子全生物组因子知之甚少。在这个 提案，我们将描述全息组（蚊子的遗传学及其相关的微生物） CX场群之间的WNV表型变化的因素。塔萨里斯。我们的总体假设是 蚊子全息组的这种变化决定了WNV感染，传播和/或 在现场传播。该假设将在以下特定目的中进行研究：（1）描述 CX的细尺度景观遗传学。美国的塔萨里斯； （2）确定 CX。 tarsalis微生物组和WNV感染，CX现场种群的传播和传播。 塔萨里斯； （3）使用复制的全基因组关联研究（PoolGWAS）来鉴定基因组基因局 与WNV感染，CX场种群中的传播和传播有关。塔萨里斯。 鉴定全息基因座影响病原体载体能力和相关遗传学的研究 人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 爆发。这项工作对于生物恐怖主义问题特别重要，因为它将提供概念 深入了解自然种群中的内在载体全息因素如何影响A的流行病学 发布了B类代理。