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（由适用提供）：流感病毒带来公共卫生风险；有效的疫苗和抗病毒药可以缓解季节性流行期间疾病的严重程度。然而，抗病毒抗性菌株和新型的人畜共患病菌株可以绕过这些古老的保护策略。了解将影响力基因组有效包装到后代病毒中所需的病毒和细胞特性将提供新颖的治疗靶标，并定义潜在的宿主范围限制因子。作为美国国立卫生研究院的博士后研究员，我开发了两种新颖的方法来可视化生产性感染期间活细胞中影响力的病毒RNA组装和运输的细胞内动力学。这些方法将与传统的生物化学技术结合使用，以阐明如何通过解决以下两个目的来包装影响力的病毒RNA片段：目标1-确定所有八个病毒RNA段选择性地将所有八个病毒RNA片段选择性地包装到进步的病毒病毒中并瞄准2-介导了介导构成源含量plasma的宿主转运的宿主成分。拟议的工作将解决影响力生物学中的许多杰出问题，由于缺乏可视化单个细胞中多个病毒RNA片段的工具，并且在生产性感染过程中跟踪活细胞中的病毒RNA运动。这些研究将提供有关如何在自然界中恢复病毒的影响，并确定可作为潜在治疗靶标的病毒RNA包装涉及的新型宿主因素。