Analysis of Novel Virus-Induced RNAs

新型病毒诱导的 RNA 分析

• 批准号: 9321119
• 负责人: CURT M HORVATH
• 金额: $ 29.87万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321119
• 关键词: Antiviral Agents; Antiviral Response; Antiviral Therapy; Atlases; Automobile Driving; Binding Sites; Biochemical; CREB1 gene; Cell Death; Cells; Cessation of life; ChIP-seq; Code; Complement; DNA Polymerase II; DNA Sequence; DNA Viruses; Data; Diagnostic; Disease Outbreaks; Ebola virus; Economics; Enterovirus; Eukaryota; Family; Gene Expression; Gene Targeting; Genes; Genetic Transcription; Genomic Segment; Genomics; Health; Health Care Costs; Herpesviridae; Herpesviridae Infections; Human; Human Genome; IRF3 gene; Immune; Immune response; Infection; Infectious Agent; Inflammatory; Influenza A virus; Interferons; Life; Mediator of activation protein; Medical; Minority; Molecular; Natural Immunity; Orthomyxoviridae; Paramyxoviridae; Paramyxovirus; Pathway interactions; Pattern; Property; RNA; RNA Viruses; Recurrence; Regulator Genes; Regulatory Pathway; Research; Role; Sendai virus; Severe Acute Respiratory Syndrome; Shapes; Signal Pathway; Signal Transduction; Simplexvirus; Site; Social Welfare; Stimulus; Structure; System; Testing; Untranslated RNA; Virus; Virus Diseases; Virus Replication; Work; adaptive immune response; adaptive immunity; antiviral immunity; base; combat; cytokine; design; experimental study; genome-wide; immune function; influenzavirus; insight; novel; novel virus; pandemic influenza; pathogen; public health relevance; response; seasonal influenza; tool; transcription factor; transcriptome sequencing; virology

 DESCRIPTION (provided by applicant): Virus infection of human cells induces rapid and dynamic gene expression that leads to the activation of downstream effector pathways that control virus replication, regulate cell death, and activate and educate subsequent innate and adaptive immune responses. Analysis of master antiviral transcription regulators IRF3 and NFκB, RNA Pol II, and Pol II-associated co-regulators before and after virus infection has revealed new features of the antiviral transcriptional response, leading to an overarching hypothesis that newly recognized virus-induced RNA products and auxiliary transcription regulators represent new aspects of antiviral immunity that have the potential to produce novel classes of antiviral therapies and diagnostic tools. These new transcription pathways will be examined in molecular detail to reveal their extent of inducibility by biomedically significant representative RNA and DNA viruses, specifically Sendai virus, influenza A virus, and herpes simplex virus. In addition their inducibility by innate antiviral signaling pathways and their potential functions in antiviral immunity will be determined. Three specific aims will use molecular and biochemical experiments to complement virological approaches and RNA-sequencing analysis to investigate the expression patterns of novel virus-induced RNAs, to determine their structures, functions, and contributions to antiviral immunity. In addition, auxiliary transcription factors in the E-Box, ETS, and CREB families that were recognized as having a role in assisting antiviral master regulators will be analyzed to determine their contributions toward driving virus-induced transcription and antiviral responses. Together these studies will provide both a broad-based and focused analysis of a newly recognized but large pool of antiviral responders that has been previously overlooked, and will identify new functional and regulatory pathways for immune control of virus infections.

 描述（由申请人提供）：人细胞的病毒感染诱导快速和动态的基因表达，导致下游效应子途径的激活，这些途径控制病毒复制、调节细胞死亡，并激活和培养随后的先天性和适应性免疫应答。对病毒感染前后主要抗病毒转录调节因子IRF 3和NFκB、RNA Pol II和Pol II相关共调节因子的分析揭示了抗病毒转录应答的新特征，导致了一个总体假设，即新发现的病毒-诱导的RNA产物和辅助转录调节因子代表了抗病毒免疫的新方面，其具有产生新型抗病毒疗法的潜力，诊断工具。这些新的转录途径将在分子上进行详细研究，以揭示其在生物医学上具有重要意义的代表性RNA和DNA病毒，特别是仙台病毒，甲型流感病毒和单纯疱疹病毒的诱导程度。此外，它们通过先天性抗病毒信号通路的诱导以及它们在抗病毒免疫中的潜在功能也将被确定。三个具体目标将使用分子和生物化学实验来补充病毒学方法和RNA测序分析，以研究新型病毒诱导的RNA的表达模式，以确定其结构，功能和对抗病毒免疫的贡献。此外，辅助转录因子的E-Box，ETS和CREB家族被认为是有一个辅助抗病毒主调节器的作用，将进行分析，以确定其对驱动病毒诱导的转录和抗病毒反应的贡献。这些研究将共同提供一个基础广泛和重点分析的新认识，但以前被忽视的抗病毒反应者的大池，并将确定新的功能和调节途径的免疫控制病毒感染。