Visualizing Influenza Viral RNA Packaging

流感病毒 RNA 包装可视化

基本信息

批准号：
8889438
负责人：
Seema S. Lakdawala
金额：
$ 15.8万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-01 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8889438
关键词：
Address Age Antiviral Agents Antiviral resistance Binding Biochemical Biological Assay Biology Bypass Cell Line Cell Nucleus Cell membrane Cells Cessation of life Chimeric Proteins Color Cytoplasm Cytoskeletal Proteins DNA-Directed RNA Polymerase Epidemic Epithelial Cells Fluorescence Resonance Energy Transfer Fluorescent in Situ Hybridization Genome Goals Green Fluorescent Proteins Hospitalization Human In Vitro Infection Influenza Integration Host Factors Knowledge Lead Length Life Location Mammalian Cell Measures Mediating Methodology Methods Microscopy Movement Nature Postdoctoral Fellow Process Property Proteins Public Health RNA RNA Transport Research Respiratory System Respiratory tract structure Risk Role Route Severity of illness System Techniques Tissues United States National Institutes of Health Vaccines Viral Viral Genes Viral Genome Viral Proteins Virion Virus Virus Diseases Virus Replication Work cell type influenza virus strain influenzavirus insight live cell imaging new therapeutic target novel pandemic disease pandemic influenza protein complex public health relevance resistant strain respiratory small molecule inhibitor therapeutic target tool viral RNA

项目摘要

DESCRIPTION (provided by applicant): Influenza viruses pose a public health risk; effective vaccines and antivirals have alleviated the severity of disease during seasonal epidemics. However, antiviral resistance strains and novel zoonotic strains of influenza can bypass these age-old protection strategies. Understanding the viral and cellular properties required for efficient packaging of the influenza genome into progeny virions will provide novel therapeutic targets and define potential host-range restriction factors. As a post-doctoral fellow at the National Institutes of Health, I have developed two novel methods to visualize the intracellular dynamics of influenza viral RNA assembly and transport in live cells during a productive infection. These methodologies will be combined with traditional biochemical techniques to elucidate how influenza viral RNA segments are packaged by addressing the following two aims: Aim 1 - Determine the mechanism by which all eight viral RNA segments selectively package into progeny virions and Aim 2 - Identify host components that mediate transport of influenza viral RNA from the nucleus to the plasma membrane. The proposed work will address many outstanding questions in influenza biology that are unanswered because of a lack of tools to visualize multiple viral RNA segments within a single cell and to track viral RNA movement in live cells during a productive infection. These studies will provide insight into how influenza viruses reassort in nature and identify novel host factors involved in viral RNA packaging that can be pursued as potential therapeutic targets.

描述（由申请人提供）：流感病毒构成公共卫生风险；有效的疫苗和抗病毒药物减轻了季节性流行期间疾病的严重性，然而，抗病毒耐药株和新型人畜共患流感株可以绕过这些古老的保护策略。将流感有效基因组包装成后代病毒颗粒所需的病毒和细胞特性将提供新的治疗靶点并确定潜在的宿主范围限制因素。两种新颖的方法可以可视化生产性感染期间活细胞中流感病毒 RNA 组装和运输的细胞内动态。这些方法将与传统的生化技术相结合，通过解决以下两个目标来阐明流感病毒 RNA 片段的包装方式：目标 1。 - 确定所有八个病毒 RNA 片段选择性包装成子代病毒体的机制，目标 2 - 识别介导流感病毒 RNA 从细胞核运输到膜质的宿主成分拟议的工作将解决流感生物学中的许多突出问题。由于缺乏工具来可视化单个细胞内的多个病毒 RNA 片段并追踪有效感染期间活细胞中病毒 RNA 的运动，这些问题尚未得到解答。这些研究将深入了解流感病毒在自然界中如何重配并识别新的宿主因子。参与病毒 RNA 包装，可作为潜在的治疗靶点。