Decoding the vRNP interaction network of influenza A viruses required for genome packaging

解码基因组包装所需的甲型流感病毒的 vRNP 相互作用网络

基本信息

项目摘要

Influenza A viruses (IAVs) are responsible for recurrent flu epidemics and occasional devastating pandemics. Their segmented genome consisting of 8 vRNAs favors evolution but requires a complex packaging mechanism that remains poorly understood. Our work and work by others indicate that the segmented genome of IAVs build a supramolecular complex held together by a redundant vRNA-vRNA interaction network and reveals a complex interplay between the vRNA packaging signals and the viral nucleoprotein (NP), suggesting that each viral ribonucleoprotein (vRNP), formed by the association of a vRNA with a polymerase complex and multiple copies of NP, has its own code. Our aim is to decode the vRNP interaction network at the vRNA and NP levels. To that goal, we will combine structural probing of vRNPs with several chemical probes and RNA-RNA crosslinking inside particles of wild type and defined mutant viruses with altered packaging determinants due to mutations in vRNAs or NP. Our project extends previous studies by combining three crucial aspects. First, by performing our structural analysis on wild type and mutant viruses, we will overcome the difficulty of identifying vRNA-vRNA and vRNA-NP interactions crucial for packaging of the IAV genome that is inherent to the redundancy of these interactions. Second, the systematic comparison of the RNA probing and RNA crosslinking data obtained with intact and disassembled viral particles will allow the unambiguous identification of interactions between adjacent vRNPs. Third, by performing RNA probing with several reagents that react with different parts of RNA, we will be able to discriminate vRNA-vRNA interactions from vRNA-NP interactions. Altogether, the our project should provide the proof of principle that specific RNA-RNA and/or RNA-protein interactions are essential for the IAV genome packaging process and shed a structural light on the plasticity of these interactions.
流感病毒(IAVS)负责复发性流行流行病和偶尔发生毁灭性的大流行病。它们的分割基因组由8个VRNA组成,有利于进化,但需要一种复杂的包装机制,仍然知之甚少。 Our work and work by others indicate that the segmented genome of IAVs build a supramolecular complex held together by a redundant vRNA-vRNA interaction network and reveals a complex interplay between the vRNA packaging signals and the viral nucleoprotein (NP), suggesting that each viral ribonucleoprotein (vRNP), formed by the association of a vRNA with a polymerase complex and multiple copies of NP,有自己的代码。我们的目的是在VRNA和NP级别上解码VRNP相互作用网络。为此,我们将将VRNP的结构探测与几个化学探针和RNA-RNA在野生型和定义的突变病毒内部颗粒内部的交联以及由于VRNA或NP突变引起的包装决定因素的改变。我们的项目通过结合三个关键方面来扩展以前的研究。首先,通过对野生型和突变病毒进行结构分析,我们将克服难以识别VRNA-VRNA和VRNA-NP相互作用对于包装IAV基因组至关重要的IAV基因组至关重要的IAV基因组。其次,通过完整和拆卸的病毒颗粒获得的RNA探测和RNA交联数据的系统比较将使相邻VRNP之间的相互作用明确鉴定。第三,通过对几种与RNA不同部分反应的试剂进行RNA探测,我们将能够区分VRNA-VRNA相互作用与VRNA-NP相互作用。总的来说,我们的项目应提供原理证明,表明特定的RNA-RNA和/或RNA-蛋白质相互作用对于IAV基因组包装过程至关重要,并为这些相互作用的可塑性提供了结构灯。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

暂无数据

数据更新时间:2024-06-01

Professor Dr. Mart...的其他基金

Characterization of the molecular mechanisms that prevent successful adaptation of avian influenza virus to the human host: the nuclear import of incoming vRNPs
阻止禽流感病毒成功适应人类宿主的分子机制的表征:传入的 vRNP 的核输入
  • 批准号:
    260781967
    260781967
  • 财政年份:
    2014
  • 资助金额:
    --
    --
  • 项目类别:
    Research Grants
    Research Grants
Regulation of the influenza A virus polymerase activity by the viral nuclear export protein (NEP)
病毒核输出蛋白(NEP)对甲型流感病毒聚合酶活性的调节
  • 批准号:
    61949751
    61949751
  • 财政年份:
    2008
  • 资助金额:
    --
    --
  • 项目类别:
    Research Grants
    Research Grants
Identification and functional characterization of cellular interaction partners of the ribonucleoprotein complex of Borna Disease Virus
博尔纳病病毒核糖核蛋白复合物细胞相互作用伴侣的鉴定和功能表征
  • 批准号:
    5449165
    5449165
  • 财政年份:
    2005
  • 资助金额:
    --
    --
  • 项目类别:
    Research Grants
    Research Grants
Funktionelle Charakterisierung des Borna Disease Virus mit Hilfe der reversen Genetik
使用反向遗传学对博尔纳病病毒进行功能表征
  • 批准号:
    5301660
    5301660
  • 财政年份:
    2001
  • 资助金额:
    --
    --
  • 项目类别:
    Research Grants
    Research Grants
Charakterisierung der molekularen Mechanismen der Resistenz gegenüber Superinfektion in Borna Disease Virus-infizierter Zellen
博尔纳病病毒感染细胞抗重复感染分子机制的表征
  • 批准号:
    5282322
    5282322
  • 财政年份:
    2000
  • 资助金额:
    --
    --
  • 项目类别:
    Research Grants
    Research Grants
Genetic predisposition and anti-IFN autoantibodies underlying severe influenza.
严重流感的遗传易感性和抗干扰素自身抗体。
  • 批准号:
    505474100
    505474100
  • 财政年份:
  • 资助金额:
    --
    --
  • 项目类别:
    Research Grants
    Research Grants
The importance of cells which survive SARS-CoV-2 infection
SARS-CoV-2 感染后存活的细胞的重要性
  • 批准号:
    509483995
    509483995
  • 财政年份:
  • 资助金额:
    --
    --
  • 项目类别:
    Research Grants
    Research Grants

相似国自然基金

HDAC9调控流感病毒vRNP乙酰化的分子机制研究
  • 批准号:
    82302495
  • 批准年份:
    2023
  • 资助金额:
    20 万元
  • 项目类别:
    青年科学基金项目
宿主RBM14蛋白促进流感病毒vRNP复合体出核转运的机制研究
  • 批准号:
    81701990
  • 批准年份:
    2017
  • 资助金额:
    20.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

Sensing Influenza A virus by RIG-I
通过 RIG-I 检测甲型流感病毒
  • 批准号:
    401088
    401088
  • 财政年份:
    2019
  • 资助金额:
    --
    --
  • 项目类别:
    Operating Grants
    Operating Grants
Ultrastructural analysis of an eight-genomic segment complex within an influenza virion
流感病毒颗粒内八基因组片段复合体的超微结构分析
  • 批准号:
    19J14928
    19J14928
  • 财政年份:
    2019
  • 资助金额:
    --
    --
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
    Grant-in-Aid for JSPS Fellows
インフルエンザウイルスvRNPが核外輸送複合体形成の場に移行するメカニズムの解明
阐明流感病毒vRNP移动至核输出复合物形成位点的机制
  • 批准号:
    17K08852
    17K08852
  • 财政年份:
    2017
  • 资助金额:
    --
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
    Grant-in-Aid for Scientific Research (C)
Modulation of Lassa Virus vRNP Activity By Host Cell Factors
宿主细胞因子对拉沙病毒 vRNP 活性的调节
  • 批准号:
    9321544
    9321544
  • 财政年份:
    2017
  • 资助金额:
    --
    --
  • 项目类别:
The host protein CLUH participates in the subnuclear transport of influenza virus ribonucleoprotein complexes.
宿主蛋白CLUH参与流感病毒核糖核蛋白复合物的亚核转运。
  • 批准号:
    15K19107
    15K19107
  • 财政年份:
    2015
  • 资助金额:
    --
    --
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
    Grant-in-Aid for Young Scientists (B)