Probing the translational dynamics of influenza virus infection.

探讨流感病毒感染的转化动力学。

• 批准号: MR/M011747/1
• 负责人: Ian Brierley
• 金额: $ 88.64万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM011747%2F1
• 关键词: Probing; translational; dynamics; influenza; virus

At the cellular level, the outcome of virus infection hinges on a battle between virus and cell for the control of the cellular biosynthetic machinery, as this ultimately determines the amount of progeny virus produced. Many viruses encode their own nucleic acid polymerases, but all are reliant on the cellular protein synthesis machinery. The ribosome therefore represents the key battleground. Using the major human and animal pathogen influenza A virus (IAV) as a model system, we will use the novel technique of ribosomal profiling to detail this conflict at a level of detail hitherto impossible. Ribosomal profiling allows the accurate determination of which mRNAs (viral or cellular) that the ribosomes are translating at a given moment; thereby defining the state of the 'frontline' in the battle for control of the cell. Our objectives are to:1. Define the cellular and viral mRNAs that are translated in virus-host cell combinations where either the virus 'wins' or where the host wins.2. To define which of the many viral mechanisms that affect cellular gene expression are and their specific targets which decide the outcome of the battle for control of the cellular translation machinery.3. Test the hypothesis that IAV specifically manipulates the ribosome to bias it towards preferential translation of viral messengers.Overall, the project will define the key events from both virus and cellular perspective that define whether an individual infected cell is productively infected; data that will aid the design of new therapeutic intervention strategies.

在细胞水平上，病毒感染的结果取决于病毒和细胞之间的战斗，以控制细胞生物合成机械，因为这最终决定了产生的后代病毒的量。许多病毒编码自己的核酸聚合酶，但所有病毒都依赖于细胞蛋白质合成机制。因此，核糖体代表了关键战场。我们将主要的人类和动物病原体流感病毒（IAV）作为模型系统，我们将使用核糖体分析的新技术来详细介绍这种冲突，迄今不可能的细节。核糖体分析可以准确确定核糖体在给定时刻转化的mRNA（病毒或细胞）的精确测定；从而在控制牢房的战斗中定义了“前线”的状态。我们的目标是：1。定义在病毒宿主宿主组合中翻译的细胞和病毒mRNA，其中病毒“获胜”或宿主获胜2。为了定义影响细胞基因表达的许多病毒机制中的哪些是及其决定控制细胞翻译机制的战斗结果的特定靶标。3。检验以下假设：IAV专门操纵核糖体以使其偏向于病毒使者的优先翻译。此外，该项目将从病毒和细胞的角度定义关键事件，这些事件定义了个体感染细胞是否有效感染；将有助于设计新的治疗干预策略的数据。

项目成果

The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis.

• DOI: 10.1261/rna.052548.115
• 发表时间: 2015-10
• 期刊: RNA (New York, N.Y.)
• 作者: Chung BY;Hardcastle TJ;Jones JD;Irigoyen N;Firth AE;Baulcombe DC;Brierley I
• 通讯作者: Brierley I

Comparative analysis of gene expression in virulent and attenuated strains of infectious bronchitis virus at sub-codon resolution

亚密码子分辨率下传染性支气管炎病毒强毒株和减毒株基因表达的比较分析

• DOI: 10.1101/612614
• 发表时间: 2019
• 作者: Dinan A

PA-X is an avian virulence factor in H9N2 avian influenza virus.

• DOI: 10.1099/jgv.0.001531
• 发表时间: 2021-03
• 期刊: The Journal of general virology
• 作者: Clements AL;Peacock TP;Sealy JE;Lee HM;Hussain S;Sadeyen JR;Shelton H;Digard P;Iqbal M
• 通讯作者: Iqbal M

Contribution of segment 3 to the acquisition of virulence in contemporary H9N2 avian influenza viruses

片段 3 对当代 H9N2 禽流感病毒毒力获得的贡献

• DOI: 10.1101/2020.05.27.119917
• 发表时间: 2020
• 作者: Clements A