Identifying determinants of HCV tropism.

确定 HCV 趋向性的决定因素。

基本信息

  • 批准号:
    6867315
  • 负责人:
  • 金额:
    $ 37.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-09-30 至 2008-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): It is estimated that 170 million people worldwide are infected with the Hepatitis C virus (HCV) and are at risk of developing chronic hepatitis or cirrhosis, the latter often leading to hepatocellular carcinoma. There is currently no vaccine and licensed therapies are associated with modest efficacies and significant toxicities. Despite the urgency of this worldwide public health problem, our basic understanding of HCV replication and pathogenesis remains poor due to a lack of key experimental models. For example, difficulties in culturing the virus in vitro and expressing native, fusogenic envelope glycoproteins have greatly limited studies of HCV tropism and entry. These are critical aspects of viral biology because the host range and pathogenesis of enveloped virus infection is largely determined by the selective interaction of viral envelope glycoproteins with cell-surface receptors. A major goal in HCV research is to understand how HCV targets the liver and by what mechanism it enters host cells. Recently, a major breakthrough in the field has been the development of retroviruses pseudotyped with HCV envelope glycoproteins that specifically mediate infection of primary hepatocytes, as well as certain other human cells. We will use this new experimental system to study HCV entry into target cells. Alterations in naturally occurring HCV envelope glycoproteins may predicate differences in receptor usage and target cell tropism in vivo. To investigate the range of HCV cellular tropism, pseudotypes incorporating envelope glycoproteins from clinical HCV isolates will be tested for their ability to enter relevant primary cells and cell lines. A functional cDNA cloning approach will be used to identify cell-surface receptors that specifically mediate HCV entry into different target cells. However, these receptors may be ubiquitously expressed and HCV targeting to different cell types may be determined by another mechanism. We recently demonstrated that L-SIGN and DC-SIGN are specific HCV-capture receptors and we will explore whether they mediate infection of target cells in trans, thereby determining HCV tropism. The major objective of our work is to identify the basic protein interactions that mediate HCV tropism, which will serve as a foundation for detailed structure/function analyses of HCV receptors and envelope glycoproteins.
描述(由申请人提供):据估计,全世界有 1.7 亿人感染丙型肝炎病毒 (HCV),并面临发展为慢性肝炎或肝硬化的风险,后者通常会导致肝细胞癌。目前还没有疫苗,而且获得许可的治疗方法疗效有限,但毒性较大。尽管这一全球性公共卫生问题十分紧迫,但由于缺乏关键的实验模型,我们对丙型肝炎病毒复制和发病机制的基本了解仍然很差。例如,体外培养病毒和表达天然融合包膜糖蛋白的困难极大地限制了HCV向性和进入的研究。这些是病毒生物学的关键方面,因为包膜病毒感染的宿主范围和发病机制很大程度上取决于病毒包膜糖蛋白与细胞表面受体的选择性相互作用。 HCV 研究的一个主要目标是了解 HCV 如何靶向肝脏以及通过什么机制进入宿主细胞。最近,该领域的一项重大突破是开发了用 HCV 包膜糖蛋白假型化的逆转录病毒,该病毒特异性介导原代肝细胞以及某些其他人类细胞的感染。我们将使用这个新的实验系统来研究丙型肝炎病毒进入靶细胞。天然存在的 HCV 包膜糖蛋白的改变可能预示着体内受体使用和靶细胞向性的差异。为了研究 HCV 细胞向性的范围,将测试掺有来自临床 HCV 分离株的包膜糖蛋白的假型进入相关原代细胞和细胞系的能力。功能性 cDNA 克隆方法将用于鉴定特异性介导 HCV 进入不同靶细胞的细胞表面受体。然而,这些受体可能普遍表达,并且HCV针对不同细胞类型的靶向可能由另一种机制决定。我们最近证明L-SIGN和DC-SIGN是特异性HCV捕获受体,我们将探讨它们是否介导反式靶细胞感染,从而确定HCV向性。我们工作的主要目标是确定介导 HCV 趋向性的基本蛋白质相互作用,这将为 HCV 受体和包膜糖蛋白的详细结构/功能分析奠定基础。

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 }}

TATJANA DRAGIC其他文献

TATJANA DRAGIC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('TATJANA DRAGIC', 18)}}的其他基金

Eliciting neutralizing antibodies against the HCV E2 envelope glycoprotein
引发针对 HCV E2 包膜糖蛋白的中和抗体
  • 批准号:
    7640900
  • 财政年份:
    2008
  • 资助金额:
    $ 37.58万
  • 项目类别:
Eliciting neutralizing antibodies against the HCV E2 envelope glycoprotein
引发针对 HCV E2 包膜糖蛋白的中和抗体
  • 批准号:
    7510088
  • 财政年份:
    2008
  • 资助金额:
    $ 37.58万
  • 项目类别:
Mechanism of HCV Internalization into Target Cells
HCV 内化至靶细胞的机制
  • 批准号:
    7140368
  • 财政年份:
    2005
  • 资助金额:
    $ 37.58万
  • 项目类别:
Mechanism of HCV Internalization into Target Cells
HCV 内化至靶细胞的机制
  • 批准号:
    6964168
  • 财政年份:
    2005
  • 资助金额:
    $ 37.58万
  • 项目类别:
Identifying determinants of HCV tropism
确定 HCV 趋向性的决定因素
  • 批准号:
    6743084
  • 财政年份:
    2003
  • 资助金额:
    $ 37.58万
  • 项目类别:
Identifying determinants of Hepatitis C Virus (HCV) tropism
确定丙型肝炎病毒 (HCV) 趋向性的决定因素
  • 批准号:
    7201634
  • 财政年份:
    2003
  • 资助金额:
    $ 37.58万
  • 项目类别:
Identifying determinants of HCV tropism.
确定 HCV 趋向性的决定因素。
  • 批准号:
    6804538
  • 财政年份:
    2003
  • 资助金额:
    $ 37.58万
  • 项目类别:
Identifying determinants of HCV tropism.
确定 HCV 趋向性的决定因素。
  • 批准号:
    7039154
  • 财政年份:
    2003
  • 资助金额:
    $ 37.58万
  • 项目类别:
Structure/Function Relationships in HIV-1 Co-Receptors
HIV-1 辅助受体的结构/功能关系
  • 批准号:
    6752008
  • 财政年份:
    1998
  • 资助金额:
    $ 37.58万
  • 项目类别:
Structure/Function Relationships in HIV-1 Co-Receptors
HIV-1 辅助受体的结构/功能关系
  • 批准号:
    6890283
  • 财政年份:
    1998
  • 资助金额:
    $ 37.58万
  • 项目类别:

相似海外基金

The 13th Canadian Symposium on Hepatitis C Virus (CSHCV)
第13届加拿大丙型肝炎病毒研讨会(CSHCV)
  • 批准号:
    487828
  • 财政年份:
    2023
  • 资助金额:
    $ 37.58万
  • 项目类别:
    Miscellaneous Programs
Characterization of key aspects of a controlled human infection model (CHIM) for hepatitis C virus (HCV) infection
丙型肝炎病毒 (HCV) 感染受控人类感染模型 (CHIM) 关键方面的表征
  • 批准号:
    478700
  • 财政年份:
    2023
  • 资助金额:
    $ 37.58万
  • 项目类别:
    Operating Grants
After the Cure: Measuring the full impacts of direct-acting antivirals for people living with HIV/hepatitis C virus coinfection in Canada
治愈之后:衡量直接作用抗病毒药物对加拿大艾滋病毒/丙型肝炎病毒合并感染者的全面影响
  • 批准号:
    469805
  • 财政年份:
    2022
  • 资助金额:
    $ 37.58万
  • 项目类别:
    Operating Grants
Perinatal care as a venue to reduce opioid overdoses and hepatitis C virus incidence (PreVenT OD HCV)
围产期护理是减少阿片类药物过量和丙型肝炎病毒发病率 (PreVenT OD HCV) 的场所
  • 批准号:
    10449670
  • 财政年份:
    2022
  • 资助金额:
    $ 37.58万
  • 项目类别:
A Simple at-home test for rapid and accurate screening for Hepatitis C Virus (HCV) exposure
简单的家庭测试,可快速、准确地筛查丙型肝炎病毒 (HCV) 暴露
  • 批准号:
    10709130
  • 财政年份:
    2022
  • 资助金额:
    $ 37.58万
  • 项目类别:
Workshop for the development of a Controlled Human Infection Model (CHIM) for hepatitis C virus (HCV) infection
丙型肝炎病毒(HCV)感染的受控人类感染模型(CHIM)开发研讨会
  • 批准号:
    460792
  • 财政年份:
    2022
  • 资助金额:
    $ 37.58万
  • 项目类别:
    Miscellaneous Programs
Rapid, Point-of-Care Diagnostics for Hepatitis C Virus
丙型肝炎病毒的快速护理点诊断
  • 批准号:
    10683045
  • 财政年份:
    2022
  • 资助金额:
    $ 37.58万
  • 项目类别:
Perinatal care as a venue to reduce opioid overdoses and hepatitis C virus incidence (PreVenT OD HCV)
围产期护理是减少阿片类药物过量和丙型肝炎病毒发病率 (PreVenT OD HCV) 的场所
  • 批准号:
    10620846
  • 财政年份:
    2022
  • 资助金额:
    $ 37.58万
  • 项目类别:
A Randomized Controlled Trial of Prophylaxis with Direct-acting Antivirals for Kidney Transplantation from Hepatitis C virus-infected donor to Uninfected Recipients (PREVENT-HCV)
直接作用抗病毒药物预防丙型肝炎病毒感染供者肾移植至未感染受者的随机对照试验 (PREVENT-HCV)
  • 批准号:
    10597168
  • 财政年份:
    2022
  • 资助金额:
    $ 37.58万
  • 项目类别:
Characterization of key aspects of a controlled human infection model (CHIM) for hepatitis C virus (HCV) infection
丙型肝炎病毒 (HCV) 感染受控人类感染模型 (CHIM) 关键方面的表征
  • 批准号:
    472508
  • 财政年份:
    2022
  • 资助金额:
    $ 37.58万
  • 项目类别:
    Operating Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了