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: 10241507
• 负责人: Jason L Rasgon
• 金额: $ 55.64万
• 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/10241507
• 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; emerging pathogen; 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 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.

了解影响病原体在病媒种群中传播的因素对了解至关重要