The role of TAX1BP1 in the innate immune response to virus infection

TAX1BP1在病毒感染先天免疫反应中的作用

基本信息

  • 批准号:
    8998913
  • 负责人:
  • 金额:
    $ 20.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-02-01 至 2018-01-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Virus infection induces an innate antiviral host response mediated by the cytoplasmic pattern recognition receptors RIG-I and MDA-5 that sense viral RNAs. RIG-I/MDA5 trigger downstream signaling events involving the mitochondrial adaptor molecule MAVS, the kinases TBK1/IKKi and the transcription factors IRF3 and IRF7. IRF3 and IRF7 directly activate the transcription of the type I interferon-(IFN) a and ß genes tha play critical antiviral roles. This pathway is tightly regulated by key inhibitory proteins that orchestrate the downregulation of antiviral signaling upon viral clearance to ensure homeostasis and prevent tissue damage and uncontrolled inflammation. Dysregulation of the balance between activation and inhibition of the RIG-I/MDA-5 pathway may result in the uncontrolled production of type I IFN that may lead to autoimmune disease. TAX1BP1 was first identified as an anti-apoptotic protein that interacts with the A20 zinc finger protein. TAX1BP1 has since been characterized as an adaptor molecule for A20, and together these two proteins inhibit the stimulus-induced activation of the NF-¿B transcription factor in inflammatory signaling pathways. We have demonstrated that TAX1BP1 and A20 also cooperate to inhibit the RIG-I/MDA-5 pathway and restrict the activation of type I IFN triggered by virus infection. However, whether the anti-apoptotic function of TAX1BP1 plays a role in the host response to virus infection is unknown. It is also unclear what the precise roles of TAX1BP1 are in vivo during the course of a respiratory virus infection such as influenza and the specific cell types where TAX1BP1 attenuates viral-induced production of proinflammatory cytokines and type I IFN. In preliminary studies we provide evidence that TAX1BP1 serves as a novel substrate of the IKKi kinase during virus infection. The phosphorylation of TAX1BP1 by IKKi triggers its proteasomal degradation and apoptotic death of virus-infected cells. Consequently, TAX1BP1-deficient cells are highly sensitive to virus-induced cell death and cytopathic effects, suggesting that the anti-apoptotic function of TAX1BP1 is unmasked by its degradation and further supporting the notion that TAX1BP1 couples antiviral signaling to cell death pathways. The central hypothesis driving the proposed investigations is that TAX1BP1 is a key regulator of innate antiviral signaling and cell survival in the context of virus infection. We will test this hypothesis experimentally with te following specific aims: (1) determine the mechanisms of IKKi-induced TAX1BP1 phosphorylation and degradation and; (2) elucidate the role of cell-type specific TAX1BP1 in regulating influenza virus infection. Completion of the proposed studies will provide important insight into the host mechanisms that are essential to restrict virus replication and may pave the way for the identification of novel antiviral drugs or vaccines for influenza infection.


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 }}

EDWARD W HARHAJ其他文献

EDWARD W HARHAJ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('EDWARD W HARHAJ', 18)}}的其他基金

KDR/VEGFR2 regulation of HTLV-1 oncogenesis and viral gene expression
KDR/VEGFR2 对 HTLV-1 肿瘤发生和病毒基因表达的调节
  • 批准号:
    10610829
  • 财政年份:
    2022
  • 资助金额:
    $ 20.25万
  • 项目类别:
KDR/VEGFR2 regulation of HTLV-1 oncogenesis and viral gene expression
KDR/VEGFR2 对 HTLV-1 肿瘤发生和病毒基因表达的调节
  • 批准号:
    10353507
  • 财政年份:
    2022
  • 资助金额:
    $ 20.25万
  • 项目类别:
AIP inhibition of IRF7 and innate antiviral signaling
AIP 抑制 IRF7 和先天抗病毒信号
  • 批准号:
    10217831
  • 财政年份:
    2021
  • 资助金额:
    $ 20.25万
  • 项目类别:
Negative regulation of innate immune signaling pathways by the selective autophagy receptor TAX1BP1
选择性自噬受体 TAX1BP1 对先天免疫信号通路的负调节
  • 批准号:
    10276931
  • 财政年份:
    2021
  • 资助金额:
    $ 20.25万
  • 项目类别:
Negative regulation of innate immune signaling pathways by the selective autophagy receptor TAX1BP1
选择性自噬受体 TAX1BP1 对先天免疫信号通路的负调节
  • 批准号:
    10797470
  • 财政年份:
    2021
  • 资助金额:
    $ 20.25万
  • 项目类别:
Negative regulation of innate immune signaling pathways by the selective autophagy receptor TAX1BP1
选择性自噬受体 TAX1BP1 对先天免疫信号通路的负调节
  • 批准号:
    10622514
  • 财政年份:
    2021
  • 资助金额:
    $ 20.25万
  • 项目类别:
AIP inhibition of IRF7 and innate antiviral signaling
AIP 抑制 IRF7 和先天抗病毒信号
  • 批准号:
    10393620
  • 财政年份:
    2021
  • 资助金额:
    $ 20.25万
  • 项目类别:
Negative regulation of innate immune signaling pathways by the selective autophagy receptor TAX1BP1
选择性自噬受体 TAX1BP1 对先天免疫信号通路的负调节
  • 批准号:
    10414107
  • 财政年份:
    2021
  • 资助金额:
    $ 20.25万
  • 项目类别:
ZFAND6 regulation of innate antiviral immunity
ZFAND6 对先天抗病毒免疫的调节
  • 批准号:
    9979076
  • 财政年份:
    2020
  • 资助金额:
    $ 20.25万
  • 项目类别:
Mechanisms of HTLV-I Tax-mediated NF-kB activation
HTLV-I Tax 介导的 NF-kB 激活机制
  • 批准号:
    8210991
  • 财政年份:
    2009
  • 资助金额:
    $ 20.25万
  • 项目类别:

相似海外基金

Development of a new generation of antiviral agents that are effective against drug-resistant viruses and prevent serious illness and sequelae.
开发新一代抗病毒药物,可有效对抗耐药病毒并预防严重疾病和后遗症。
  • 批准号:
    23K18186
  • 财政年份:
    2023
  • 资助金额:
    $ 20.25万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
A versatile structure-based therapeutic platform for development of VHH-based antitoxin and antiviral agents
一个多功能的基于结构的治疗平台,用于开发基于 VHH 的抗毒素和抗病毒药物
  • 批准号:
    10560883
  • 财政年份:
    2023
  • 资助金额:
    $ 20.25万
  • 项目类别:
Genetically encoded bicyclic peptide libraries for the discoveryof novel antiviral agents
用于发现新型抗病毒药物的基因编码双环肽库
  • 批准号:
    10730692
  • 财政年份:
    2021
  • 资助金额:
    $ 20.25万
  • 项目类别:
Design and synthesis of nucleosides to develop antiviral agents and oligonucleotide therapeutics
设计和合成核苷以开发抗病毒药物和寡核苷酸疗法
  • 批准号:
    21K06459
  • 财政年份:
    2021
  • 资助金额:
    $ 20.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Genetically encoded bicyclic peptide libraries for the discoveryof novel antiviral agents
用于发现新型抗病毒药物的基因编码双环肽库
  • 批准号:
    10189880
  • 财政年份:
    2021
  • 资助金额:
    $ 20.25万
  • 项目类别:
Computer-aided identification and synthesis of novel broad-spectrum antiviral agents
新型广谱抗病毒药物的计算机辅助鉴定和合成
  • 批准号:
    2404261
  • 财政年份:
    2020
  • 资助金额:
    $ 20.25万
  • 项目类别:
    Studentship
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
  • 批准号:
    10222540
  • 财政年份:
    2020
  • 资助金额:
    $ 20.25万
  • 项目类别:
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
  • 批准号:
    10669717
  • 财政年份:
    2020
  • 资助金额:
    $ 20.25万
  • 项目类别:
Association between sedentary lifestyle and liver cancer development in hepatitis C patients treated with direct-acting antiviral agents
接受直接抗病毒药物治疗的丙型肝炎患者久坐的生活方式与肝癌发展之间的关系
  • 批准号:
    20K10713
  • 财政年份:
    2020
  • 资助金额:
    $ 20.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
  • 批准号:
    10174522
  • 财政年份:
    2020
  • 资助金额:
    $ 20.25万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了