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Bacterial effectors as probes to study (+) RNA virus-host cell biology

细菌效应子作为研究 ( ) RNA 病毒-宿主细胞生物学的探针

基本信息

批准号：
9089955
负责人：
Brett D. Lindenbach
金额：
$ 20.81万
依托单位：
YALE UNIVERSITY
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：
2015-06-15 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9089955
关键词：
Address Affect Autophagocytosis Award Bacteria Bacterial Infections Biochemical Biological Cell Communication Cells Cellular biology Collaborations Collection Coxiella Coxiella burnetii Cytosol Data Dengue Virus Development Enzymes Eukaryotic Cell Family Flaviviridae Follow-Up Studies Funding Future Genes Genetic Golgi Apparatus Health Hepatitis C virus Immune response Integration Host Factors Legionella pneumophila Legionnaires&apos Disease Mammalian Cell Maps Membrane Protein Traffic Methods Operative Surgical Procedures Outcome Study Pathogenesis Pathway interactions Pharmacopoeias Phenotype Proteins Proteomics Qualifying RNA Interference RNA Viruses RNA interference screen Reagent Reproducibility Research Research Proposals Role Specificity Staging Transmembrane Transport United States National Institutes of Health Virus Virus Replication Work Yellow fever virus base cellular targeting follow-up genome-wide genome-wide analysis high throughput screening innovation insight interest knock-down member novel strategies pathogen prevent protein protein interaction research study screening success tool virus host interaction yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): All viruses depend on their host cells for replication. However, many aspects of virus-host cell interaction - such as the role of membrane trafficking in (+) RNA virus replication - are still poorly understood, in part due to a lack of sufficiently precise and powerful tools. This Exploratory and Developmental Research Proposal explores a new strategy to identify virus-host cell interaction by employing a large collection of bacterial effector proteins as cell biological probes, based on the observation that these proteins frequently target the same cellular pathways used by (+) RNA viruses. Because bacterial effector proteins are genetically encoded enzymes that have evolved to manipulate host cell biology with high specificity and activity, they have distinct advantages over other reagents for probing virus-host interaction, such as RNAi or pharmacological agents. By using a high-throughput screening approach, we will express a panel of 435 bacterial effector proteins to manipulate host cell biology, and examine how these perturbations affect the replication of hepatitis C virus, dengue virus, and yellow fever virus, three representative members of the Flaviviridae. Hits will then be prioritized for further mechanistic characterization and follow up studies. Our preliminary data demonstrate feasibility of this approach and provide interesting leads for future experiments. The outcome of these studies will provide proof of concept for our strategy, will generate a set of unique tools to study an important group of (+) RNA viruses, and will collaboratively synergize with ongoing research into bacterial effector mechanisms. We envision a future experimental niche wherein virologists and cell biologists will be able to utiliz a toolkit of bacterial effector proteins to probe many different biological questions.