Characterizing the Role of Encapsidated Host Ribosomes in Alphavirus Infectivity

表征衣壳宿主核糖体在甲病毒感染性中的作用

• 批准号: 8687964
• 负责人: Kevin Joseph Sokoloski
• 金额: $ 5.51万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8687964
• 关键词: Alphavirus; Animal Model; Antiviral Agents; Biological; Biological Assay; Biology; Birds; Cell Line; Cells; Culicidae; Data; Derivation procedure; Disease Outbreaks; Drosophila genus; Elements; Epidemic; Exhibits; Gene Expression; Genetic; Genotype; Goals; Growth; Health; Human; Infection; Integration Host Factors; Invertebrates; Label; Mammalian Cell; Mass Spectrum Analysis; Metabolic; Microinjections; Modeling; Molecular; Morphology; Nucleocapsid; Population; Protein Biosynthesis; RNA; RNA Viruses; Readiness; Reagent; Relative (related person); Replicon; Ribosomal RNA; Ribosomes; Role; Scientist; Severities; Sindbis Virus; Site; Source; Structural Models; Structure; Sucrose; System; Training; Translations; Vaccines; Viral; Viral Genes; Viral Genome; Viral Proteins; Virion; Virus; Virus Diseases; Work; base; career; comparative; crosslink; density; design; experience; fitness; interdisciplinary approach; member; mortality; mutant; novel; novel strategies; nucleoside analog; particle; public health relevance; success; therapeutic vaccine; tissue/cell culture; tomography; transmission process; vaccine development; vector; vector mosquito

DESCRIPTION (provided by applicant): The Alphaviruses are a group of related RNA viruses that are cyclically transmitted between mammalian / avian hosts and vector mosquitos. Members of the genus Alphavirus are recognized for their epidemic potential and several exhibit high mortality rates upon infection. Contemporary outbreaks of alphaviruses and the ongoing geographical distribution of vector-competent mosquitos towards naive populations underscore the need for effective antiviral targets and vaccine strategies. Previous studies have characterized alphaviral particles produced in mammalian and avian cells; however particles produced in mosquito cells have been largely overlooked. Examination of mosquito derived Sindbis virus (SINV) has indicated that host ribosomal components are incorporated into the viral particles. Characterization of this phenomenon revealed that host ribosomes are incorporated into mammalian derived particles as well, but at a rate less than that observed for mosquito derived particles. Interestingly, the levels of ribosome encapsidation were found to correlate with the number of infectious particles. The work detailed in this proposal uses a multidisciplinary approach consisting of virological, molecular, structural and model organism studies to characterize the determinants leading to and the biological role of ribosome encapsidation. This proposal is designed to provide a unique training experience that will enable those involved in its conceptualization and implementation to continue towards a career as an independent scientist.

描述(申请人提供)：甲型病毒是一组相关的RNA病毒，在哺乳动物/禽类宿主和媒介蚊子之间循环传播。甲型病毒属的成员因其流行潜力而被公认，其中一些成员在感染后表现出很高的死亡率。目前甲型病毒的暴发和具有媒介能力的蚊子目前在地理上向幼稚人群分布，突显了有效的抗病毒目标和疫苗战略的必要性。以前的研究已经确定了哺乳动物和鸟类细胞中产生的甲型病毒颗粒的特征；然而，在蚊子细胞中产生的颗粒在很大程度上被忽视了。对蚊源辛德比斯病毒(SINV)的检测表明，宿主核糖体成分被整合到病毒颗粒中。对这一现象的表征表明，宿主核糖体也被整合到哺乳动物来源的颗粒中，但速度低于观察到的蚊子来源的颗粒。有趣的是，核糖体包裹的水平被发现与感染颗粒的数量相关。本提案中详细介绍的工作采用了多学科方法，包括病毒学、分子学、结构和模式生物体研究，以表征导致核糖体包埋的决定因素和核糖体包埋的生物学作用。这项提议旨在提供一种独特的培训经验，使参与构思和实施的人能够继续从事独立科学家的职业生涯。