Circular RNAs in HSV1 infection and antiviral immunity

HSV1感染和抗病毒免疫中的环状RNA

基本信息

  • 批准号:
    10495211
  • 负责人:
  • 金额:
    $ 6.73万
  • 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:
    2021-09-24 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary Circular (circ) RNAs are a recently described class of RNAs generated by backsplicing of adjacent exons, whose expression is altered in several disease states and some of the few viral infections in which they have been studied. Functionally, circRNAs rarely direct protein synthesis but have been linked to the sequestration of microRNAs and RNA binding proteins (RNA-BPs). CircRNAs were recently implicated in controlling the activation of double-stranded (ds) RNA-activated eIF2α kinase PKR by providing an abundant pool of inhibitory short duplex RNA sequences. Bound inactive PKR can be rapidly mobilized by if RNase L is activated, resulting in endoribonucleolytic cleavage of circRNAs. Generated by both RNA virus replication and dsDNA virus transcription from opposing genome strands, dsRNA is a potent pathogen associated molecular pattern (PAMP) whose recognition by PKR and the OAS/RNase L pathway leads to an abrupt defensive shutdown of mRNA translation to thwart viral protein synthesis. In addition to possible virus and circRNA -specific interactions, the potential of circRNAs to calibrate dsRNA responses therefore suggests a broad significance to virus biology. However, precisely how the infected cell circRNA population responds to herpes simplex type 1 (HSV1) infection and impacts virus reproduction remains unknown and represents a significant knowledge gap. The overall goal of this proposal is to understand how circRNAs contribute to HSV1 infection and antiviral immunity. Our preliminary data in HSV1-infected cells indicate that circRNAs are protected from degradation by the viral endoribonuclease vhs and are in fact selectively upregulated through a mechanism dependent on the viral immediate early protein ICP27. We also find that PKR activation is dependent on RNase L function, suggesting that circRNAs are important inhibitors of PKR in HSV1 infection that must be degraded for a full antiviral response. These data are consistent with the novel hypothesis that HSV1 actively manipulates this class of host RNAs to evade cell intrinsic antiviral defenses and preserve protein synthesis and viral replication. This proposal will be divided into two aims to fully understand 1) how HSV1 shapes the infected cell circRNAome and 2) the functional impact of these alterations. These studies will reveal how circRNAs are manipulated by HSV1 and their importance in infection and immunity to a medically important human pathogen. Ultimately, this work could lead to new strategies for treating a wide variety of viral infections and have significant implications for our understanding of infection, host defenses and circRNA biology.
项目摘要 环状RNA是最近描述的一类通过相邻外显子的反向剪接产生的RNA, 其表达在几种疾病状态和少数几种病毒感染中发生改变, 本文研究了在功能上,circRNA很少指导蛋白质合成,但与螯合有关。 microRNA和RNA结合蛋白(RNA-BPs)。CircRNA最近被认为与控制 通过提供丰富的抑制性PKR库激活双链(ds)RNA激活的eIF 2 α激酶PKR, 短双链RNA序列。如果RNase L被激活, 导致circRNA的内切核糖核酸裂解。由RNA病毒复制和dsDNA产生 病毒转录从相反的基因组链,dsRNA是一种有效的病原体相关分子模式 (PAMP),其被PKR和OAS/RNase L途径识别导致突然的防御性关闭。 mRNA翻译以阻碍病毒蛋白质合成。除了可能的病毒和circRNA特异性 因此,circRNA校准dsRNA反应的潜力表明, 病毒生物学然而,受感染的细胞circRNA群体对1型单纯疱疹病毒的反应 单纯疱疹病毒1型(HSV 1)感染及其对病毒繁殖的影响仍然是未知的,这代表了一个重大的知识缺口。 该提案的总体目标是了解circRNA如何促进HSV 1感染, 抗病毒免疫我们在HSV 1感染细胞中的初步数据表明,circRNA被保护, 并且事实上通过一种机制选择性地上调 依赖于病毒立即早期蛋白ICP 27。我们还发现PKR的激活依赖于 RNase L功能,表明circRNA是HSV 1感染中PKR的重要抑制剂, 降解以产生全面的抗病毒反应。这些数据与新的假设一致,即HSV 1主动地 操纵这类宿主RNA以逃避细胞内在的抗病毒防御并保持蛋白质合成 和病毒复制。本提案将分为两个目的,以充分了解1)HSV 1如何塑造 感染的细胞circRNAome和2)这些改变的功能影响。这些研究将揭示 circRNA由HSV 1操纵,并且它们在感染和免疫中的重要性对医学上重要的免疫系统起着重要作用。 人类病原体最终,这项工作可能会导致治疗各种病毒感染的新策略 并对我们理解感染、宿主防御和circRNA生物学具有重要意义。

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)

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

{{ 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 }}

Hannah Marion Burgess其他文献

Hannah Marion Burgess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('Hannah Marion Burgess', 18)}}的其他基金

Cellular RNAs in anti-viral immunity to HSV1
细胞 RNA 在 HSV1 抗病毒免疫中的作用
  • 批准号:
    10553861
  • 财政年份:
    2021
  • 资助金额:
    $ 6.73万
  • 项目类别:
Cellular RNAs in anti-viral immunity to HSV1
细胞 RNA 在 HSV1 抗病毒免疫中的作用
  • 批准号:
    10471808
  • 财政年份:
    2021
  • 资助金额:
    $ 6.73万
  • 项目类别:
Circular RNAs in HSV1 infection and antiviral immunity
HSV1感染和抗病毒免疫中的环状RNA
  • 批准号:
    10354703
  • 财政年份:
    2021
  • 资助金额:
    $ 6.73万
  • 项目类别:
Cellular RNAs in anti-viral immunity to HSV1 - Resubmission - 1
细胞 RNA 在 HSV1 抗病毒免疫中的作用 - 重新提交 - 1
  • 批准号:
    10218718
  • 财政年份:
    2021
  • 资助金额:
    $ 6.73万
  • 项目类别:
Circular RNAs in HSV1 infection and antiviral immunity
HSV1感染和抗病毒免疫中的环状RNA
  • 批准号:
    10553859
  • 财政年份:
    2021
  • 资助金额:
    $ 6.73万
  • 项目类别:

相似海外基金

Regulation of RIG-I mediated antiviral response upon influenza A virus infection
RIG-I介导的甲型流感病毒感染抗病毒反应的调节
  • 批准号:
    494286
  • 财政年份:
    2023
  • 资助金额:
    $ 6.73万
  • 项目类别:
    Operating Grants
Activation of the DNA-PK-dependent antiviral response as a novel cancer immunotherapy
激活 DNA-PK 依赖性抗病毒反应作为一种新型癌症免疫疗法
  • 批准号:
    10364056
  • 财政年份:
    2022
  • 资助金额:
    $ 6.73万
  • 项目类别:
ADAR1-mediated antiviral response in Zika virus (ZIKV) infection
ADAR1 介导的寨卡病毒 (ZIKV) 感染抗病毒反应
  • 批准号:
    10621913
  • 财政年份:
    2022
  • 资助金额:
    $ 6.73万
  • 项目类别:
ADAR1-mediated antiviral response in Zika virus (ZIKV) infection
ADAR1 介导的寨卡病毒 (ZIKV) 感染抗病毒反应
  • 批准号:
    10373627
  • 财政年份:
    2022
  • 资助金额:
    $ 6.73万
  • 项目类别:
Activation of the DNA-PK-dependent antiviral response as a novel cancer immunotherapy
激活 DNA-PK 依赖性抗病毒反应作为一种新型癌症免疫疗法
  • 批准号:
    10553146
  • 财政年份:
    2022
  • 资助金额:
    $ 6.73万
  • 项目类别:
Mechanisms of IgE-mediated regulation of monocyte antiviral response pathways
IgE介导的单核细胞抗病毒反应途径的调节机制
  • 批准号:
    10640247
  • 财政年份:
    2021
  • 资助金额:
    $ 6.73万
  • 项目类别:
Interplay between AMPK and Hippo Signaling Regulates Ocular Antiviral Response to Zika virus infection
AMPK 和 Hippo 信号传导之间的相互作用调节眼部对寨卡病毒感染的抗病毒反应
  • 批准号:
    10322026
  • 财政年份:
    2021
  • 资助金额:
    $ 6.73万
  • 项目类别:
Mechanisms of IgE-mediated regulation of monocyte antiviral response pathways
IgE 介导的单核细胞抗病毒反应途径调节机制
  • 批准号:
    10438876
  • 财政年份:
    2021
  • 资助金额:
    $ 6.73万
  • 项目类别:
Antiviral response coupled with transposon derepression in Alzheimer's disease and aging
抗病毒反应与转座子去抑制在阿尔茨海默病和衰老中的作用
  • 批准号:
    10629440
  • 财政年份:
    2021
  • 资助金额:
    $ 6.73万
  • 项目类别:
Epigenetic Control of Mucosal IRF1/IFN-III Antiviral Response by Enhancer-like Promoter and its Coding lncRNA
增强子样启动子及其编码lncRNA对粘膜IRF1/IFN-III抗病毒反应的表观遗传控制
  • 批准号:
    10373575
  • 财政年份:
    2021
  • 资助金额:
    $ 6.73万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了