The role of TRIM2 and SIRPA in New World Arenavirus entry

TRIM2 和 SIRPA 在新世界沙粒病毒进入中的作用

基本信息

  • 批准号:
    10362439
  • 负责人:
  • 金额:
    $ 44.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-05-23 至 2027-04-30
  • 项目状态:
    未结题

项目摘要

New world hemorrhagic fever arenaviruses (NWAs), such as Junín virus, are rodent-transmitted viruses that cause ~30% mortality when they zoonose into humans. The mechanism by the NWAs induce disease is still not certain, although it likely includes induction of high levels of cytokines by infected sentinel cells of the immune system, leading to endothelia and thrombocyte dysfunction and neurological disease. Survivors of Junín infection develop strong humoral immune responses, suggesting that controlling infection at early times post-infection is critical for virus clearance. Although an effective Junín virus vaccine has decreased disease incidence, sporadic cases of this as well as the other known and novel NWAs for which there are no vaccines or effective therapeutics still occur. It is well-established that the clade B pathogenic NWAs bind to transferrin receptor 1 and other receptors on the cell surface, but the steps leading to their entry from an acidic cellular compartment are not well-determined. We recently performed a siRNA screen with pseudotyped viruses bearing a pathogenic Junín glycoprotein with the goal of finding host genes involved in entry that could serve as therapeutic targets. We found that TRIM2, a member of the tripartite motif family that includes well-known members of the host's intrinsic defense against viral infections, limits NWA endocytosis into cells. By probing the TRIM2 interactome for other host proteins that block NWA infection, we discovered that SIRPA, a cell surface protein that inhibits macrophage phagocytosis of tumor and dead cells and erythrocytes, also decreases infection. Importantly, SIRPA, unlike TRIM2, inhibits infection by various human pathogenic viruses that require trafficking to an acidic compartment, including VSV, Zika virus, LCMV and Ebola and SARS-Cov-2 pseudoviruses. Our data suggest that TRIM2 and SIRPA act at the viral entry/internalization step. These finding suggests that there are common mechanisms that regulate virus endocytosis and phagocytosis. We propose here to further investigate the overlap between virus-mediated endocytosis and phagocytosis in vitro, ex vivo and in vivo in three aims that will 1) investigate the overlap in the NWA entry and phagocytosis pathways; 2) determine where TRIM2/SIRPA inhibition of infection occurs; and 3) use TRIM2, SIRPA and other relevant knockout mice to probe the roles of these proteins in cell-type specific and in vivo infection by replication-competent NWAs. In addition to providing mechanistic insight into the entry of NWAs into cells, these studies have the potential of increasing our understanding as to how host factors limit infection and could lead to new approaches to therapeutic intervention.
新世界出血热沙粒病毒(NWAs),如Junín病毒,是啮齿动物传播的

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 }}

SUSAN R ROSS其他文献

SUSAN R ROSS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('SUSAN R ROSS', 18)}}的其他基金

Interplay between reverse transcription and host restriction
逆转录与宿主限制之间的相互作用
  • 批准号:
    10607086
  • 财政年份:
    2023
  • 资助金额:
    $ 44.11万
  • 项目类别:
The role of TRIM2 and SIRPA in New World Arenavirus entry
TRIM2 和 SIRPA 在新世界沙粒病毒进入中的作用
  • 批准号:
    10625278
  • 财政年份:
    2022
  • 资助金额:
    $ 44.11万
  • 项目类别:
Role of DDX41 in HSC development and MDS/AML
DDX41 在 HSC 发育和 MDS/AML 中的作用
  • 批准号:
    10216402
  • 财政年份:
    2021
  • 资助金额:
    $ 44.11万
  • 项目类别:
Role of DDX41 in HSC development and MDS/AML
DDX41 在 HSC 发育和 MDS/AML 中的作用
  • 批准号:
    10373097
  • 财政年份:
    2021
  • 资助金额:
    $ 44.11万
  • 项目类别:
Role of APOBEC3 in in vivo Restriction of Retrovirus Infection
APOBEC3 在体内限制逆转录病毒感染中的作用
  • 批准号:
    9054058
  • 财政年份:
    2016
  • 资助金额:
    $ 44.11万
  • 项目类别:
Role of APOBEC3 in in vivo Restriction of Retrovirus Infection
APOBEC3 在体内限制逆转录病毒感染中的作用
  • 批准号:
    9176518
  • 财政年份:
    2016
  • 资助金额:
    $ 44.11万
  • 项目类别:
Role of DNA sensors in host anti-retroviral defense
DNA传感器在宿主抗逆转录病毒防御中的作用
  • 批准号:
    9172791
  • 财政年份:
    2016
  • 资助金额:
    $ 44.11万
  • 项目类别:
APOBEC3-mediated damage of host genomic DNA in vivo
APOBEC3 介导的体内宿主基因组 DNA 损伤
  • 批准号:
    8822043
  • 财政年份:
    2015
  • 资助金额:
    $ 44.11万
  • 项目类别:
Gordon Research Conference on "Infections of the nervous system: Pathogenesis and Worldwide Impact1"
戈登研究会议“神经系统感染:发病机制和全球影响1”
  • 批准号:
    8986297
  • 财政年份:
    2015
  • 资助金额:
    $ 44.11万
  • 项目类别:
TRIM2, a novel host factor that restricts New World Arenavirus infection
TRIM2,一种限制新世界沙粒病毒感染的新型宿主因子
  • 批准号:
    8852547
  • 财政年份:
    2014
  • 资助金额:
    $ 44.11万
  • 项目类别:

相似海外基金

A novel motility system driven by two classes of bacterial actins MreB
由两类细菌肌动蛋白 MreB 驱动的新型运动系统
  • 批准号:
    22KJ2613
  • 财政年份:
    2023
  • 资助金额:
    $ 44.11万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
The structural basis of plasmid segregation by bacterial actins
细菌肌动蛋白分离质粒的结构基础
  • 批准号:
    342887
  • 财政年份:
    2016
  • 资助金额:
    $ 44.11万
  • 项目类别:
    Operating Grants
The structural basis for plasmid segregation by bacterial actins
细菌肌动蛋白分离质粒的结构基础
  • 批准号:
    278338
  • 财政年份:
    2013
  • 资助金额:
    $ 44.11万
  • 项目类别:
    Operating Grants
Cytoplasmic Actins in Maintenance of Muscle Mitochondria
细胞质肌动蛋白在维持肌肉线粒体中的作用
  • 批准号:
    8505938
  • 财政年份:
    2012
  • 资助金额:
    $ 44.11万
  • 项目类别:
Differential Expression of the Diverse Plant Actins
多种植物肌动蛋白的差异表达
  • 批准号:
    7931495
  • 财政年份:
    2009
  • 资助金额:
    $ 44.11万
  • 项目类别:
Studies on how actins and microtubules are coordinated and its relevancy.
研究肌动蛋白和微管如何协调及其相关性。
  • 批准号:
    19390048
  • 财政年份:
    2007
  • 资助金额:
    $ 44.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Suppression of Arabidopsis Reproductive Actins
拟南芥生殖肌动蛋白的抑制
  • 批准号:
    6655612
  • 财政年份:
    2003
  • 资助金额:
    $ 44.11万
  • 项目类别:
Suppression of Arabidopsis Reproductive Actins
拟南芥生殖肌动蛋白的抑制
  • 批准号:
    6546977
  • 财政年份:
    2003
  • 资助金额:
    $ 44.11万
  • 项目类别:
Interaction of myosin with monomeric actins
肌球蛋白与单体肌动蛋白的相互作用
  • 批准号:
    5311554
  • 财政年份:
    2001
  • 资助金额:
    $ 44.11万
  • 项目类别:
    Priority Programmes
STRUCTURE/INTERACTIONS OF ACTINS AND ACTIN-BINDING PROTEIN
肌动蛋白和肌动蛋白结合蛋白的结构/相互作用
  • 批准号:
    6316669
  • 财政年份:
    2000
  • 资助金额:
    $ 44.11万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了