Flavivirus cellular tropisms driving dissemination and transmission in mosquito vectors

黄病毒细胞向性驱动蚊媒传播和传播

• 批准号: 10341228
• 负责人: Kendra Marie Quicke
• 金额: $ 7.23万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10341228
• 关键词: Address; Aedes; Affect; Animal Model; Area; Automobile Driving; Bite; Brain; Case Fatality Rates; Cells; Cellular Tropism; Centers for Disease Control and Prevention (U.S.); Characteristics; Clone Cells; Colorado; Congenital Abnormality; Culicidae; Cytomegalovirus; Data; Dendritic Cells; Dengue Hemorrhagic Fever; Dengue Infection; Dengue Shock Syndrome; Dengue Virus; Development; Disease; Educational workshop; Effectiveness; Endothelial Cells; Engineering; Epidemic; Extravasation; Feeding behaviors; Fellowship; Fetal Development; Flavivirus; Flavivirus Infections; Foundations; Genome; Grant; Head; Hemocytes; Icterus; Immune; Individual; Infection; Insect Vectors; Institution; Knowledge; Laboratories; Liquid substance; Liver; MicroRNAs; Microcephaly; Midgut; Multiple Organ Failure; Mus; Neurons; Neurotropism; Organ; Pathology; Population; Predisposition; Public Health; Reagent; Research; Research Training; Risk; Role; Salivary Glands; System; Techniques; Testing; Tissues; Training; Training Activity; Tropism; Universities; Vascular Permeabilities; Viral; Viral Pathogenesis; Virus; Virus Diseases; Virus Replication; Work; Writing; Yellow Fever; Yellow fever virus; Zika Virus; career; cell type; data tools; differential expression; experimental study; feeding; human model; improved; infant infection; interest; lymph nodes; macrophage; mosquito-borne; nerve stem cell; next generation sequencing; post-doctoral training; responsible research conduct; skills; success; symposium; tissue tropism; tool; transmission process; vector; vector competence; vector mosquito; viral transmission

Project Summary/Abstract The research objectives of this fellowship are to determine the cellular tropisms of three mosquito-borne flaviviruses of public health importance – Zika virus, dengue virus and yellow fever virus – within their Aedes aegypti vectors and to define the roles of specific cell populations in viral dissemination and transmission. The aims are to 1) identify the specific cell populations critical for viral dissemination from the midgut to the salivary glands, and 2) define the impact of specific tissue tropisms on mosquito feeding behavior and viral transmission. Aim 1 will be accomplished by generating microRNA (miRNA) expression profiles for midgut, hemocyte and neuronal cell populations and selecting miRNAs that are highly differentially expressed in each population. We will confirm infection of cells expressing these miRNAs and generate cell-specific, miRNA-restricted viruses containing target sequences for cell-specific miRNAs to probe the roles of each cell type in viral dissemination. Aim 2 will be accomplished by using miRNA-restricted viruses to determine the effect of neuronal cell and salivary gland infection on mosquito feeding behaviors and subsequent transmission of the virus by observing infected mosquitoes feeding on mice and testing mice for the presence of virus. The data and tools produced by this work could aid the development of transmission control strategies that target viral replication in specific cell populations within the vector. Research and postdoctoral training activities will be undertaken at both Colorado State University and the Centers for Disease Control and Prevention in Fort Collins, CO. The sponsor and co- sponsor laboratories have complimentary research interests and facilities that will promote the success of this project. In addition to research, the training plan includes completion of coursework in next generation sequencing experiment and analysis, grant writing, and responsible conduct of research; participation in supervisory training; and attendance at various workshops, seminars and conferences to improve writing, presentation and career building skills.

项目概要/摘要 该奖学金的研究目标是确定三种蚊媒的细胞趋向性 伊蚊体内具有公共卫生重要性的黄病毒——寨卡病毒、登革热病毒和黄热病病毒 埃及伊蚊载体并定义特定细胞群在病毒传播和传播中的作用。这 目的是 1) 确定对病毒从中肠到唾液传播至关重要的特定细胞群 腺体，2) 定义特定组织向性对蚊子摄食行为和病毒传播的影响。 目标 1 将通过生成中肠、血细胞和中肠的 microRNA (miRNA) 表达谱来实现。 神经元细胞群体并选择在每个群体中高度差异表达的 miRNA。我们 将确认表达这些 miRNA 的细胞的感染并生成细胞特异性、miRNA 限制的病毒 含有细胞特异性 miRNA 的靶序列，可探测每种细胞类型在病毒传播中的作用。 目标 2 将通过使用 miRNA 限制性病毒来确定神经元细胞和唾液的作用来实现 通过观察感染者，了解腺体感染对蚊子摄食行为和随后病毒传播的影响 蚊子以老鼠为食并测试老鼠是否存在病毒。本工作产生的数据和工具 可以帮助开发针对特定细胞中病毒复制的传播控制策略 向量内的种群。研究和博士后培训活动将在科罗拉多州和科罗拉多州进行 州立大学和科罗拉多州柯林斯堡的疾病控制和预防中心。主办方和合作方 赞助实验室拥有互补的研究兴趣和设施，这将促进这一项目的成功 项目。除了研究之外，培训计划还包括完成下一代的课程作业 测序实验和分析、资助写作以及负责任的研究行为；参与 监督培训；以及参加各种研讨会、研讨会和会议以提高写作水平， 演讲和职业建设技能。

项目成果

Early Adoption of Longitudinal Surveillance for SARS-CoV-2 among Staff in Long-Term Care Facilities: Prevalence, Virologic and Sequence Analysis.

• DOI: 10.1128/spectrum.01003-21
• 发表时间: 2021-12-22
• 期刊: Microbiology spectrum
• 影响因子: 3.7
• 作者: Gallichotte EN;Quicke KM;Sexton NR;Fitzmeyer E;Young MC;Janich AJ;Dobos K;Pabilonia KL;Gahm G;Carlton EJ;Ebel GD;Ehrhart N
• 通讯作者: Ehrhart N