HBGA receptors in host cell entry and infection of norovirus

HBGA受体在诺如病毒进入宿主细胞和感染中的作用

基本信息

  • 批准号:
    9182813
  • 负责人:
  • 金额:
    $ 48.98万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-12-01 至 2019-11-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): We seek to understand the interactions between Human noroviruses (HuNoVs) and their Histo-blood group antigen (HBGA) receptors in the attachment/penetration into host cells and potentially triggering conformational dynamics of the viral capsid and genome release in the early stage of viral infection. HuNoVs in the Caliciviridae family are the major cause of nonbacterial gastroenteritis worldwide. The highly contagious HuNoVs can rapidly spread among the population through contaminated food, water and person-to-person contact in confined spaces, such as cruises, hotels, schools, hospitals and other long-term health care facilities. There are approximately 21 million cases of infection in ~1,500 HuNoVs outbreaks in the United States annually, which causes severe economic loss to society and threatens human health. Despite this serious public health concern, knowledge about the infection mechanism and pathogenesis of HuNoVs is limited due to the lack of a permissive cell line. Our past decade studies showed a strong association of HBGAs as a susceptibility factor in NoV infection, and therefore further studies to seek direct evidence on HBGAs as a receptor of NoVs are necessary. In this R01 application, we will use the recently discovered primate Tulane virus (TV) as the model system to fulfill our goals because of its close genetic and structural similarities to HuNoVs, the availability of an established cultivation system, and the fact that TV also utilizes HBGAs as receptors. We will first test the HBGA requirement in TV infection in cell cultures by performing blocking or inhibition experiments using HBGA-specific blocking reagents. We also will study the roles of HBGAs in the attachment and/or penetration of TV entry into host cells. Furthermore, we will test a novel hypothesis of HBGA-triggered dynamic change of TV capsid on viral genome release to initiate infection. This hypothesis is based on our recent observation of conformational changes of TV following interaction with HBGAs. Finally, we will validate these findings using a reverse genetic system of TV by mutagenesis studies in attempt to determine the hot spots in the capsid protein responsible for these interactions. We also aim to develop the TV culture system into a useful surrogate for antiviral screening/evaluation against HuNoVs. The proposed studies in this application will be performed by collaboration between two research teams on structural biology (Wen Jiang, PI) and molecular virology (Xi Jiang, co-PI) with an excellent collaboration track record in the past. We are confident that we will make a rapid progress in fulfilling our aims.
描述(由申请方提供):我们试图了解人诺如病毒(HuNoV)与其组织血型抗原(HBGA)受体在附着/渗透到宿主细胞中以及在病毒感染早期可能触发病毒衣壳构象动力学和基因组释放中的相互作用。杯状病毒科中的HuNoV是全世界非细菌性胃肠炎的主要原因。具有高度传染性的HuNoV可以通过受污染的食物、水以及在游轮、酒店、学校、医院和其他长期卫生保健设施等密闭空间中的人与人之间的接触在人群中迅速传播。美国每年约有1,500起HuNoV暴发,约有2100万例感染病例,给社会造成严重的经济损失,并威胁人类健康。尽管存在这种严重的公共卫生问题,但由于缺乏允许的细胞系,关于HuNoV的感染机制和发病机制的知识有限。我们过去十年的研究表明,HBGAs作为NoV感染的易感因素具有很强的相关性,因此有必要进一步研究以寻求HBGAs作为NoV受体的直接证据。在这个R 01应用中,我们将使用最近发现的灵长类动物杜兰病毒(TV)作为模型系统来实现我们的目标,因为它与HuNoV具有密切的遗传和结构相似性, 系统,以及电视也利用HBGAs作为受体的事实。我们将首先通过使用HBGA特异性阻断试剂进行阻断或抑制实验来测试细胞培养物中TV感染的HBGA要求。我们还将研究HBGAs在TV进入宿主细胞的附着和/或渗透中的作用。此外,我们将测试HBGA引发的TV衣壳动态变化对病毒基因组释放以启动感染的新假设。这一假设是基于我们最近观察到的构象变化的电视与HBGAs的相互作用。最后,我们将验证这些发现,使用反向遗传系统的电视诱变研究,试图确定热点的衣壳蛋白负责这些相互作用。我们还旨在将TV培养系统开发成用于针对HuNoV的抗病毒筛选/评估的有用替代物。本申请中的拟议研究将由结构生物学(Wen Jiang,PI)和分子病毒学(Xi Jiang,co-PI)两个研究团队合作进行,这两个研究团队过去有着良好的合作记录。我们相信,我们将在实现我们的目标方面取得迅速进展。

项目成果

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科研奖励数量(0)
会议论文数量(0)
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Wen Jiang其他文献

Wen Jiang的其他文献

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{{ truncateString('Wen Jiang', 18)}}的其他基金

Affinity purification of cross-ß fibrils using immobilized thioflavin
使用固定化硫代黄素对交叉原纤维进行亲和纯化
  • 批准号:
    10646061
  • 财政年份:
    2023
  • 资助金额:
    $ 48.98万
  • 项目类别:
Engineering In Vivo Chimeric Antigen Receptor Macrophages (CARMs) using mRNA-exosomes for Cancer Immunotherapy
使用 mRNA-外泌体工程体内嵌合抗原受体巨噬细胞 (CARM) 用于癌症免疫治疗
  • 批准号:
    10740743
  • 财政年份:
    2023
  • 资助金额:
    $ 48.98万
  • 项目类别:
A Phagocytosis Modulating Nanomedicine for Targeted Breast Cancer Immunotherapy
用于靶向乳腺癌免疫治疗的吞噬调节纳米药物
  • 批准号:
    10381905
  • 财政年份:
    2021
  • 资助金额:
    $ 48.98万
  • 项目类别:
Therapeutic targeting of multiple glioblastoma phagocytosis checkpoints using a novel bispecific antibody
使用新型双特异性抗体靶向治疗多个胶质母细胞瘤吞噬检查点
  • 批准号:
    10428596
  • 财政年份:
    2021
  • 资助金额:
    $ 48.98万
  • 项目类别:
Therapeutic targeting of multiple glioblastoma phagocytosis checkpoints using a novel bispecific antibody
使用新型双特异性抗体靶向治疗多个胶质母细胞瘤吞噬检查点
  • 批准号:
    10212046
  • 财政年份:
    2021
  • 资助金额:
    $ 48.98万
  • 项目类别:
Therapeutic targeting of multiple glioblastoma phagocytosis checkpoints using a novel bispecific antibody
使用新型双特异性抗体靶向治疗多个胶质母细胞瘤吞噬检查点
  • 批准号:
    10609925
  • 财政年份:
    2021
  • 资助金额:
    $ 48.98万
  • 项目类别:
Renal Cell Carcinoma Surveillance by Immuno-Lipoplex Nanoparticle Platform
通过免疫脂质体纳米颗粒平台监测肾细胞癌
  • 批准号:
    10544876
  • 财政年份:
    2020
  • 资助金额:
    $ 48.98万
  • 项目类别:
Renal Cell Carcinoma Surveillance by Immuno-Lipoplex Nanoparticle Platform
通过免疫脂质体纳米颗粒平台监测肾细胞癌
  • 批准号:
    10044277
  • 财政年份:
    2020
  • 资助金额:
    $ 48.98万
  • 项目类别:
A Phagocytosis Modulating Nanomedicine for Targeted Breast Cancer Immunotherapy
用于靶向乳腺癌免疫治疗的吞噬调节纳米药物
  • 批准号:
    9805697
  • 财政年份:
    2019
  • 资助金额:
    $ 48.98万
  • 项目类别:
HBGA receptors in host cell entry and infection of norovirus
HBGA受体在诺如病毒进入宿主细胞和感染中的作用
  • 批准号:
    8967560
  • 财政年份:
    2014
  • 资助金额:
    $ 48.98万
  • 项目类别:

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