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: 10677536
• 负责人: Jason L Rasgon
• 金额: $ 52.48万
• 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/10677536
• 关键词: Address; Affect; Attention; Bacteria; Biological Markers; Bioterrorism; Categories; Category B pathogen; Cessation of life; Chromosome Mapping; 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; Invaded; Knowledge; Laboratories; 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; biomarker identification; candidate validation; cost; disorder control; emerging pathogen; experimental study; fungus; genome wide association study; genomic locus; in vivo; insight; interest; microbial; microbiome; microbiome components; microorganism; migration; mosquito-borne pathogen; 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.

了解影响病媒种群中病原体传播的因素对于理解这一点至关重要 疾病发病动态、新病原体引入风险评估策略的制定和 开发可用于有效控制目标的传播生物标志物。虽然小说 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 病毒 (WNV) 是美国最广泛传播的蚊媒病原体。由于其 1999 年，西尼罗河病毒在美国全面传播，确诊人数超过 50,000 人 病例和 2,000 多人死亡。最有效的实验室媒介是跗库蚊，已被确定为 美国西部一个非常重要的载体。我们最近的工作表明， Cx的遗传结构。跗节和西尼罗河病毒在美国西部的入侵模式；中的一个 第一项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，媒介能力的变化归因于蚊子之间的遗传差异 菌株或个体。然而，没有任何有机体是孤立存在的。生物体是一个由以下组成的群落 宿主及其相关微生物（细菌、真菌和病毒）共同构成了全生物组。 关于影响野外病原体入侵的蚊子全生物组因素知之甚少。在这个 建议，我们将描绘全基因组（蚊子及其相关微生物的遗传学） 不同野外 Cx 群体中 WNV 表型变异的潜在因素。跗节。我们的总体假设是 蚊子全基因组的变异决定了西尼罗河病毒感染、传播和/或 领域内的传播。该假设将在以下具体目标中进行研究：（1）描绘 Cx 的精细景观遗传学。跗节在美国； (2) 确定之间的关系 CX。跗节微生物组和西尼罗河病毒在 Cx 野外人群中的感染、传播和传播。 跗骨; (3) 使用复制的全基因组关联研究 (PoolGWAS) 来识别基因组位点 与西尼罗河病毒在 Cx 野外人群中的感染、传播和传播有关。跗节。 影响病原载体能力的全基因组位点鉴定及相关遗传研究 人群之间的差异对于了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 深入了解自然群体中的内在向量全基因组因素如何影响流行病学 发布B类代理。

项目成果

Temperature affects viral kinetics and vectorial capacity of Aedes aegypti mosquitoes co-infected with Mayaro and Dengue viruses.

温度影响与 Mayaro 和登革热病毒共感染的埃及伊蚊的病毒动力学和传播能力。

• 发表时间: 2024-02-19
• 影响因子: 3.2
• 作者: Terradas, Gerard;Manzano;Vanalli, Chiara;Werling, Kristine;Cattadori, Isabella M;Rasgon, Jason L
• 通讯作者: Rasgon, Jason L

Eilat virus (EILV) causes superinfection exclusion against West NILE virus (WNV) in a strain specific manner in Culex tarsalis mosquitoes.

埃拉特病毒 (EILV) 在跗库蚊中以毒株特异性方式引起对西尼罗河病毒 (WNV) 的重复感染排除。

• 发表时间: 2023-05-25
• 作者: Joseph, Renuka E;Bozic, Jovana;Werling, Kristine L;Urakova, Nadya;Rasgon, Jason L
• 通讯作者: Rasgon, Jason L