Role of cell tropism for Zika virus transmission and pathogenesis

细胞向性在寨卡病毒传播和发病机制中的作用

• 批准号: 9268283
• 负责人: Gregory David Ebel
• 金额: $ 22.73万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9268283
• 关键词: 3' Untranslated Regions; Adult; Aedes; Americas; Arboviruses; Attenuated; Attenuated Live Virus Vaccine; Attenuated Vaccines; Binding; Biology; Brazil; Breeding; Cell Line; Cells; Cellular Tropism; Centers for Disease Control and Prevention (U.S.); Chikungunya virus; Chile; Clinical; Collaborations; Colorado; Competence; Complementary DNA; Congenital Abnormality; Country; Culicidae; Data; Development; Disease Outbreaks; Easter Island; Employee Strikes; Engineering; Epidemic; Epithelial; Epithelium; Female; Fetus; Flavivirus; French Polynesia; Genes; Genitourinary system; Genome; Geography; Goals; Gonadal structure; Human; In Vitro; Interruption; Island; Knock-out; Knowledge; Lead; Leukocytes; Mammalian Cell; Mediating; Messenger RNA; MicroRNAs; Microcephaly; Midgut; Molecular Virology; Mothers; Mus; Neurons; Neuropathogenesis; Organism; Pathogenesis; Pathway interactions; Patients; Pattern; Phase; Population; Pregnancy; Process; Production; Puerto Rican; Puerto Rico; RNA Interference; Reporting; Research; Role; Salivary Glands; Seminal; Serum; Sexual Partners; Sexual Transmission; Specificity; Syndrome; Testing; Time; Tissues; Tropism; Uganda; Universities; Untranslated Regions; Vaccines; Viral; Viremia; Virus; Virus Replication; West Nile virus; Work; Zika Virus; base; cell type; design; disorder prevention; experience; in utero; in vivo; insight; male; miRNA expression profiling; mutant; novel; novel virus; transmission process; vector; viral RNA; viral transmission; virus pathogenesis

This proposal is for an R21, Role of cell tropism for pathogenesis and vector competence of Zika virus. The project is a collaboration between Drs. Gregory Ebel (Colorado State University) and Aaron Brault (Centers for Disease Control and Prevention). The overall goal of this research is to understand how different cells contribute to sexual and mosquito transmission of Zika. Our overall approach to this project involves using a newly developed cDNA clone of the PRABC59 strain of Zika virus (from a Puerto Rican patient, 2015) that has been engineered to express miRNA target sequences. These sequences restrict virus replication in organism- tissue- and cell-specific manners due to binding of the cognate miRNA to viral RNA and subsequent degradation of the vRNA by the RNAi pathway. Aim 1 focuses on developing appropriate constructs and evaluating efficacy using cell lines and primary cultures. Aim 2 moves the project into an in vivo testing phase using Ag129 mice, which are available at CDC as a breeding colony, and Aedes aegypti mosquitoes, which are available at CSU as several newly established colonies. The proposed research leverages extensive preliminary data and a developing collaboration that brings together expertise in molecular virology, arboviral pathogenesis and vector biology.

该提议是针对R21的，这是细胞卓越在发病机理中的作用和Zika病毒的载体能力。这 项目是Drs之间的合作。格雷戈里·埃贝尔（Gregory Ebel）（科罗拉多州立大学）和亚伦·布鲁特（Aaron Brault） 疾病控制和预防）。这项研究的总体目标是了解不同的细胞如何 有助于Zika的性和蚊子传播。我们对该项目的总体方法涉及使用 新开发的Prabc59 Zika病毒菌株的cDNA克隆（来自波多黎各患者，2015年） 已设计以表达miRNA目标序列。这些序列限制了生物体中的病毒复制 由于同源miRNA与病毒RNA的结合，组织和细胞特异性的举止以及随后的 RNAi途径对VRNA的降解。 AIM 1专注于开发适当的结构并使用细胞系和主要的评估功效 文化。 AIM 2使用AG129小鼠将项目移至体内测试阶段，可在CDC上获得 作为一个繁殖殖民地和埃德斯埃及埃及蚊子，在CSU上可用，如几个新建立 殖民地。 拟议的研究利用了广泛的初步数据和发展的合作 分子病毒学，弧病毒发病机理和载体生物学方面的专业知识。