Demonstrating the mechanism of Nairovirus translation strategy

展示内罗病毒翻译策略的机制

基本信息

  • 批准号:
    10291623
  • 负责人:
  • 金额:
    $ 42.3万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-01 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

Abstract: Crimean Congo hemorrhagic fever is a tick born, highly contagious, viral illness with high mortality rates in humans. There is no treatment for this viral disease at present. We recently reported that Crimean Congo hemorrhagic fever virus nucleocapsid protein (CCHFV N protein) has two distinct RNA binding sites in the stalk and head domains. The RNA binding site located in the head domain non-specifically binds to the single strand RNA of viral or nonviral origin. However, the RNA binding site located in the stalk domain specifically binds to the double strand panhandle structure formed by the base pairing of highly conserved and complementary nucleotides at the 5’ and 3’ termini of the viral genome. Interestingly the viral mRNA 5’ UTR also folds into a panhandle-like secondary structure, which is also specifically recognized by the stalk domain of N protein. The interaction between N protein and viral mRNA 5’ UTR facilitates the translation of downstream open reading frame (ORF). The majority of eukaryotic mRNA translation is m7G cap dependent and is initiated by the assembly of eIF4F cap binding complex, composed of three initiation factors eIF4E, eIF4A and eIF4G. Our preliminary data shows that N protein mediated translation strategy does not require the assembly of eIF4F complex but the structural integrity of individual components of this complex is required for this viral translation mechanism. This published data suggests that CHFV N protein highly likely lures the host translation apparatus for the preferential translation of viral mRNA during the course of infection, to boost the translation of viral mRNA in the infected cell. We will use multifaceted experimental avenues to test the hypothesis that CCHFV N protein interacts with the components of eIF4F complex to selectively engage the 40S ribosomal subunits on the viral mRNA 5’ UTR. Since ribosome loading on mRNA is a critical rate limiting step in eukaryotic translation, CCHFV N protein likely helps the viral transcripts at this critical step by selectively engaging the host cell ribosomes on viral mRNA 5’ UTR. This selective ribosome loading likely helps viral transcripts by avoiding the competition from host cell transcripts for the same host translation machinery. We will determine whether CCHFV N protein mediated translation strategy selectively facilitates the translation of viral mRNA during the course of infection.
摘要:克里米亚刚果出血热是一种蜱虫性、高度传染性、病毒性疾病,死亡率高 在人类中的比率。目前还没有治疗这种病毒性疾病的方法。我们最近报道说,克里米亚刚果 出血热病毒核衣壳蛋白(CCHFV N蛋白)在其细胞核中有两个不同的RNA结合位点, 茎域和头域。位于头部结构域中的RNA结合位点非特异性地结合至单核苷酸。 病毒或非病毒来源RNA链。然而,RNA结合位点特异性地位于茎结构域, 结合到由高度保守的碱基配对形成的双链柄状结构, 在病毒基因组的5 '和3'末端的互补核苷酸。有趣的是, 也折叠成锅柄状二级结构,该结构也被 N蛋白。N蛋白和病毒mRNA 5 'UTR之间的相互作用促进了下游转录因子的翻译。 开放阅读框(ORF)。大多数真核生物mRNA翻译是m7G帽依赖性的,并且启动于 通过组装eIF4F帽结合复合物,由eIF4E、eIF4A和eIF4G三个起始因子组成。 我们的初步数据表明,N蛋白介导的翻译策略不需要eIF4F的组装 复合物,但这种复合物的各个组分的结构完整性是这种病毒所必需的。 翻译机制这一已发表的数据表明,CHFV N蛋白很可能诱导宿主翻译 在感染过程中优先翻译病毒mRNA的装置,以促进 病毒mRNA在受感染的细胞中。我们将使用多方面的实验途径来测试假设, CCHFV N蛋白与eIF4F复合物的组分相互作用以选择性地接合40S核糖体 在病毒mRNA 5'UTR上的亚基。由于核糖体在mRNA上的加载是细胞增殖的关键限速步骤, 真核翻译,CCHFV N蛋白可能通过选择性地帮助病毒转录在这个关键步骤 接合病毒mRNA 5 'UTR上的宿主细胞核糖体。这种选择性的核糖体装载可能有助于病毒 通过避免来自宿主细胞转录本的竞争来获得相同的宿主翻译机制。我们 将确定CCHFV N蛋白介导的翻译策略是否选择性地促进 病毒mRNA在感染过程中。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Modulations in the host cell proteome by the hantavirus nucleocapsid protein.
  • DOI:
    10.1371/journal.ppat.1011925
  • 发表时间:
    2024-01
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
  • 通讯作者:
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Mohammad A Mir其他文献

Infant Sleep Positioning and SIDS: A Hospital Based Interventional Study
婴儿睡眠姿势与婴儿猝死综合征:一项基于医院的干预性研究
  • DOI:
    10.1203/00006450-199904020-00636
  • 发表时间:
    1999-04-01
  • 期刊:
  • 影响因子:
    3.100
  • 作者:
    Bharath Srivatsa;Alvin N Eden;Mohammad A Mir
  • 通讯作者:
    Mohammad A Mir

Mohammad A Mir的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Mohammad A Mir', 18)}}的其他基金

Preferential translation of host cell factors by hantavirus nucleocapsid protein
汉坦病毒核衣壳蛋白优先翻译宿主细胞因子
  • 批准号:
    9292026
  • 财政年份:
    2017
  • 资助金额:
    $ 42.3万
  • 项目类别:
Characterization of hantavirus N protein-mediated translation mechanism
汉坦病毒N蛋白介导的翻译机制的表征
  • 批准号:
    8218779
  • 财政年份:
    2012
  • 资助金额:
    $ 42.3万
  • 项目类别:
Characterization of hantavirus N protein-mediated translation mechanism
汉坦病毒N蛋白介导的翻译机制的表征
  • 批准号:
    8424961
  • 财政年份:
    2012
  • 资助金额:
    $ 42.3万
  • 项目类别:
Identification and characterization of inhibitors for hantavirus replication
汉坦病毒复制抑制剂的鉴定和表征
  • 批准号:
    8309019
  • 财政年份:
    2011
  • 资助金额:
    $ 42.3万
  • 项目类别:
Identification and characterization of inhibitors for hantavirus replication
汉坦病毒复制抑制剂的鉴定和表征
  • 批准号:
    8508844
  • 财政年份:
    2011
  • 资助金额:
    $ 42.3万
  • 项目类别:
Identification and characterization of inhibitors for hantavirus replication
汉坦病毒复制抑制剂的鉴定和表征
  • 批准号:
    8150134
  • 财政年份:
    2011
  • 资助金额:
    $ 42.3万
  • 项目类别:
MECHANICS OF HANTAVIRAL NUCLEOCAPSID PROTEIN MEDIATED TRANSLATION INITIATION OF
汉病毒核衣壳蛋白介导的翻译起始机制
  • 批准号:
    8168405
  • 财政年份:
    2010
  • 资助金额:
    $ 42.3万
  • 项目类别:
Role of Cellular P-bodies and Hantavirus Nucleocapsid Protein in Viral mRNA "cap
细胞P体和汉坦病毒核衣壳蛋白在病毒mRNA“帽”中的作用
  • 批准号:
    7701441
  • 财政年份:
    2009
  • 资助金额:
    $ 42.3万
  • 项目类别:
Role of Cellular P-bodies and Hantavirus Nucleocapsid Protein in Viral mRNA "cap
细胞P体和汉坦病毒核衣壳蛋白在病毒mRNA“帽”中的作用
  • 批准号:
    7897814
  • 财政年份:
    2009
  • 资助金额:
    $ 42.3万
  • 项目类别:

相似海外基金

Impact of alternative polyadenylation of 3'-untranslated regions in the PI3K/AKT cascade on microRNA
PI3K/AKT 级联中 3-非翻译区的替代多聚腺苷酸化对 microRNA 的影响
  • 批准号:
    573541-2022
  • 财政年份:
    2022
  • 资助金额:
    $ 42.3万
  • 项目类别:
    University Undergraduate Student Research Awards
How do untranslated regions of cannabinoid receptor type 1 mRNA determine receptor subcellular localisation and function?
1 型大麻素受体 mRNA 的非翻译区如何决定受体亚细胞定位和功能?
  • 批准号:
    2744317
  • 财政年份:
    2022
  • 资助金额:
    $ 42.3万
  • 项目类别:
    Studentship
MICA:Synthetic untranslated regions for direct delivery of therapeutic mRNAs
MICA:用于直接递送治疗性 mRNA 的合成非翻译区
  • 批准号:
    MR/V010948/1
  • 财政年份:
    2021
  • 资助金额:
    $ 42.3万
  • 项目类别:
    Research Grant
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
  • 批准号:
    10019570
  • 财政年份:
    2019
  • 资助金额:
    $ 42.3万
  • 项目类别:
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
  • 批准号:
    10223370
  • 财政年份:
    2019
  • 资助金额:
    $ 42.3万
  • 项目类别:
Translational Control by 5'-untranslated regions
5-非翻译区域的翻译控制
  • 批准号:
    10455108
  • 财政年份:
    2019
  • 资助金额:
    $ 42.3万
  • 项目类别:
Synergistic microRNA-binding sites, and 3' untranslated regions: a dialogue of silence
协同的 microRNA 结合位点和 3 非翻译区:沉默的对话
  • 批准号:
    255762
  • 财政年份:
    2012
  • 资助金额:
    $ 42.3万
  • 项目类别:
    Operating Grants
Analysis of long untranslated regions in Nipah virus genome
尼帕病毒基因组长非翻译区分析
  • 批准号:
    20790351
  • 财政年份:
    2008
  • 资助金额:
    $ 42.3万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Search for mRNA elements involved in the compatibility between 5' untranslated regions and coding regions in chloroplast translation
寻找参与叶绿体翻译中 5 非翻译区和编码区之间兼容性的 mRNA 元件
  • 批准号:
    19370021
  • 财政年份:
    2007
  • 资助金额:
    $ 42.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Post-transcriptional Regulation of PPAR-g Expression by 5'-Untranslated Regions
5-非翻译区对 PPAR-g 表达的转录后调控
  • 批准号:
    7131841
  • 财政年份:
    2006
  • 资助金额:
    $ 42.3万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了