Novel Translational Control Mechanisms in Host Range Restriction of Poxvirus

痘病毒宿主范围限制的新型翻译控制机制

基本信息

  • 批准号:
    10463680
  • 负责人:
  • 金额:
    $ 42.24万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-22 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

All viruses rely on host translational machinery for protein synthesis. As such, translation control constitutes a universal host defense against viruses. A new understanding on how host regulates translation in response to viral infection and how viruses evade this host response will provide fundamental insight into viral pathogenesis and benefit the development of new antiviral strategies. Poxviruses include some dangerous emerging pathogens as well as some promising vaccine vectors. Unlike many other viruses, poxvirus host range is not affected by the entry step but restricted by intracellular processes. Particularly, cellular translational control pathways have a profound impact on poxvirus host range, and poxvirus inhibitors of these pathways could manifest as critical host-range factors. The best-known example is PKR-mediated control of translation initiation and its antagonism by two vaccinia virus (VACV) host-range proteins E3 and K3. Much less is understood about a PKR-independent pathway targeted by two critical VACV host-range proteins, K1 and C7. VACV with deletion in both K1 and C7 fails to replicate in most mammalian cells due to a shut-off of viral and host protein synthesis. Intriguingly, the translational shut-off is independent of PKR and RNaseL and appears not to involve any translation initiation factors. A paralogous pair of interferon-stimulated genes, SAMD9 and SAMD9L (SAMD9&L), were recently identified by us and others as the specific targets of K1 and C7. However, how they regulate protein synthesis and restrict poxvirus host range is unknown and is the focus of this proposal. We have made sustained contributions to the understanding of K1/C7 and their cellular targets for over a decade, including the determination of the structures of K1/C7 and the identification of SAMD9L as a cellular target of K1/C7. In addition, we have obtained compelling preliminary data that led to our novel hypotheses, which will be addressed separately with the following specific aims. Aim 1. To determine how SAMD9 is activated to inhibit protein synthesis. Aim 2. To determine how activated SAMD9 inhibits protein synthesis. Aim 3. To determine the molecular basis underlying the host species-specific SAMD9&L inhibition by OPXV inhibitors.
所有的病毒都依赖宿主的翻译机制来合成蛋白质。因此,翻译

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)

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Junpeng Deng其他文献

Junpeng Deng的其他文献

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{{ truncateString('Junpeng Deng', 18)}}的其他基金

Developing small molecule inhibitors for modulating cytokine IL18 activities
开发调节细胞因子 IL18 活性的小分子抑制剂
  • 批准号:
    10393624
  • 财政年份:
    2021
  • 资助金额:
    $ 42.24万
  • 项目类别:
Developing small molecule inhibitors for modulating cytokine IL18 activities
开发调节细胞因子 IL18 活性的小分子抑制剂
  • 批准号:
    10226420
  • 财政年份:
    2021
  • 资助金额:
    $ 42.24万
  • 项目类别:
Structure function studies of a molecular complex for generating viral membrane
用于生成病毒膜的分子复合物的结构功能研究
  • 批准号:
    10170273
  • 财政年份:
    2020
  • 资助金额:
    $ 42.24万
  • 项目类别:
Novel Translational Control Mechanisms in Host Range Restriction of Poxvirus
痘病毒宿主范围限制的新型翻译控制机制
  • 批准号:
    10382081
  • 财政年份:
    2020
  • 资助金额:
    $ 42.24万
  • 项目类别:
Novel Translational Control Mechanisms in Host Range Restriction of Poxvirus
痘病毒宿主范围限制的新型翻译控制机制
  • 批准号:
    10680408
  • 财政年份:
    2020
  • 资助金额:
    $ 42.24万
  • 项目类别:
Novel Translational Control Mechanisms in Host Range Restriction of Poxvirus
痘病毒宿主范围限制的新型翻译控制机制
  • 批准号:
    10675831
  • 财政年份:
    2020
  • 资助金额:
    $ 42.24万
  • 项目类别:
Novel Translational Control Mechanisms in Host Range Restriction of Poxvirus
痘病毒宿主范围限制的新型翻译控制机制
  • 批准号:
    10267770
  • 财政年份:
    2020
  • 资助金额:
    $ 42.24万
  • 项目类别:
Structure function studies of a molecular complex for generating viral membrane
用于生成病毒膜的分子复合物的结构功能研究
  • 批准号:
    10057852
  • 财政年份:
    2020
  • 资助金额:
    $ 42.24万
  • 项目类别:
Non-vesicular lipid transport by poxvirus A6 protein
痘病毒 A6 蛋白的非囊泡脂质转运
  • 批准号:
    9379762
  • 财政年份:
    2017
  • 资助金额:
    $ 42.24万
  • 项目类别:
Structure-function studies on a key signaling module from interleukin 17 receptor
白细胞介素17受体关键信号模块的结构-功能研究
  • 批准号:
    8771995
  • 财政年份:
    2014
  • 资助金额:
    $ 42.24万
  • 项目类别:

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