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Influenza Viral RNA Synthesis and Processing

流感病毒 RNA 合成和加工

基本信息

批准号：
7576108
负责人：
Laura Lynn Newcomb
金额：
$ 12.41万
依托单位：
CALIFORNIA STATE UNIV SAN BERNARDINO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-03-01 至 2011-02-28
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Project Summary: My career objective is to run a molecular virology laboratory at a research and education institute initially focused on elucidating the biochemical mechanisms required for influenza viral replication. The proposed research aims to define the roles of viral and cellular proteins required for influenza viral RNA synthesis and processing. Experiments are designed to probe function of mutant viral proteins and identify virus-host interactions involved in influenza virus propagation. Specific Aim 1 will examine the RNA synthesis and processing activities of mutant influenza proteins, both in vitro and in vivo, to define the role of viral - viral and viral - host protein interactions essential to viral propagation. Experiments will probe the role of influenza nucleocapsid protein (NP) and RNA dependent RNA polymerase (RdRP) contacts, and two identified viral - host interactions; the influenza RdRP with the C-terminal domain (CTD) of cellular RNA polymerase II, and influenza NP with host cellular splicing and export factor UAP56. Specific Aim 2 will identify host splicing and nuclear export factors hijacked by influenza viral mRNAs. Known cellular export pathways will be examined for their function during influenza virus infection. To discover novel cellular nuclear export pathways, cis regions within the viral mRNAs that are required for viral mRNA export will be defined through mutagenesis screening. The discovered RNA element(s) will then be utilized to identify cellular proteins which specifically bind the viral RNA. Viral mRNA splicing and export is an area poorly understood for influenza viruses. The proposed research will provide assays to screen and discover compounds which inhibit influenza virus infection and may lay foundation for development of antiviral therapies. Further, this research has potential to discover novel cellular RNA processing and nuclear export pathways. Relevance: Influenza is a pressing health issue for humans. The best line of defense for a rapidly emerging highly pathogenic virus is anti-viral medications, although resistance makes the search for new anti-viral targets a constant struggle. The proposed research aims to understand molecular mechanisms required for influenza viral infection with the intent to lay the foundation for development of novel anti-viral therapies.

描述（由申请人提供）：项目摘要：我的职业目标是在一个研究和教育机构运行一个分子病毒学实验室，最初专注于阐明流感病毒复制所需的生化机制。拟议的研究旨在确定流感病毒RNA合成和加工所需的病毒和细胞蛋白的作用。设计实验以探测突变病毒蛋白的功能并鉴定流感病毒繁殖中涉及的病毒-宿主相互作用。具体目标1将在体外和体内检查突变流感蛋白的RNA合成和加工活性，以确定病毒-病毒和病毒-宿主蛋白相互作用对病毒繁殖至关重要的作用。实验将探索流感病毒核衣壳蛋白（NP）和RNA依赖性RNA聚合酶（RdRP）接触的作用，以及两种已鉴定的病毒-宿主相互作用;流感病毒RdRP与细胞RNA聚合酶II的C-末端结构域（CTD），以及流感病毒NP与宿主细胞剪接和输出因子UAP 56。具体目标2将确定宿主剪接和核输出因子劫持流感病毒的mRNA。将检查已知的细胞输出途径在流感病毒感染期间的功能。为了发现新的细胞核输出途径，将通过诱变筛选来定义病毒mRNA输出所需的病毒mRNA内的顺式区域。发现的RNA元件随后将用于鉴定特异性结合病毒RNA的细胞蛋白。病毒mRNA剪接和输出是流感病毒知之甚少的领域。这项研究将为筛选和发现抑制流感病毒感染的化合物提供检测方法，并可能为开发抗病毒治疗奠定基础。此外，这项研究有可能发现新的细胞RNA加工和核输出途径。相关性：流感是人类面临的一个紧迫的健康问题。快速出现的高致病性病毒的最佳防线是抗病毒药物，尽管耐药性使寻找新的抗病毒靶点成为一场持续的斗争。这项研究旨在了解流感病毒感染所需的分子机制，为开发新型抗病毒疗法奠定基础。