Studies of hepatitis C virus polarized cell entry and host factor requirements
丙型肝炎病毒极化细胞进入和宿主因子要求的研究
基本信息
- 批准号:7707255
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-05-15 至 2011-04-30
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsAnimal ModelAntiviral AgentsAntiviral TherapyAreaBaculovirusesCell Culture TechniquesCell PolarityCellsDevelopmentEffectivenessEventFamilyFibrosisFlaviviridaeFoundationsFutureGenotypeGoalsHCV screeningHeadHepatitis C virusHepatocyteHumanIndividualIntegration Host FactorsInterferonsInvestigationLaboratoriesLaboratory ResearchLife Cycle StagesLiver FailureLiver diseasesMusNaturePhasePopulationProcessResearchRetroviridaeRiceSystemTechniquesTight JunctionsTime StudyTransplantationUnited StatesViralViral ProteinsVirionVirusVirus ReplicationWorkanti-hepatitis Cbasecareerclaudin-1 proteincombatdesigneffective therapyfascinategraft failureimprovedinsightliver transplantationnovelpolarized cellpreventresearch studyvirology
项目摘要
Hepatitis C virus (HCV) is the leading cause of liver disease in the United States. With no specific anti-HCV
therapies, the cun-ently employed interferon-based treatment is inadequate, as it has severe side effects and
is only effective in half of the major genotype infected individuals. The research proposed in this application
is aimed at furthering the understanding the HCV replication mechanisms, with the ultimate goal of . .
uncovering novel antiviral targets. In the past, I have studied how HCV replication is regulated, how viral
proteins interact with each other and cellular factors, and helped establish systems to study HCV in cell
culture. Currently, my research is focused on the earliest events in the viral life cycle involving entry into the
host cell, which are poorly understood processes. In particular, although several host factors have been
implicated as involved in HCV entry, litt|e is know as to how they are utilized by the virus. Our recent
identification ofthe tight junction protein, claudin-1 (CLDN1), as essential for this process was a major development in this field. This discovery has opened-up a whole new view of HCV cell entry, as the involvement of CLDN1 in cell polarity strongly suggests that the polarized nature of an hepatocyte may influence how HCV enter a cell. This proposal describes experiments to; 1) study HCV entry into polarized cells, 2) define how the virion interacts with and utilizes the known HCV entry factors, and 3) perform additional screens for HCV entry factors able to render both human and murine cells infectable with HCV.
Such investigations will provide greater, much needed insight in HCV replication, as well as lay the
foundation for future studies of replication of HCV and other related viruses.
丙型肝炎病毒(HCV)是美国肝脏疾病的主要原因。无特异性抗HCV
虽然干扰素治疗是一种有效的治疗方法,但目前采用的基于干扰素的治疗是不够的,因为它具有严重的副作用,
仅对一半的主要基因型感染个体有效。本申请中提出的研究
旨在进一步了解HCV的复制机制,最终目标是。.
发现新的抗病毒靶点。在过去,我研究了HCV的复制是如何被调节的,病毒是如何
蛋白质相互作用和细胞因子,并帮助建立系统,研究丙型肝炎病毒在细胞中,
文化目前,我的研究主要集中在病毒生命周期中最早的事件,包括进入
宿主细胞,这是知之甚少的过程。特别是,尽管已经有几个主机因素
与HCV进入有关,|我们知道病毒如何利用它们。我们最近
紧密连接蛋白Claudin-1(CLDN 1)的鉴定是该领域的一个主要进展。这一发现开辟了HCV细胞进入的全新视角,因为CLDN 1参与细胞极性强烈表明肝细胞的极化性质可能影响HCV如何进入细胞。该提案描述了以下实验:1)研究HCV进入极化细胞,2)定义病毒体如何与已知的HCV进入因子相互作用并利用已知的HCV进入因子,3)对能够使人和鼠细胞都感染HCV的HCV进入因子进行额外的筛选。
这样的研究将提供更大的,急需的深入了解丙型肝炎病毒的复制,以及奠定
为今后研究HCV和其他相关病毒的复制奠定了基础。
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 }}
Matthew J Evans其他文献
Enforcing Metal-Arene Interactions in Bulky p-Terphenyl Bis(anilide) Complexes of Group 2 Metals (Be-Ba): Potential Precursors for Low-Oxidation-State Alkaline Earth Metal Systems.
强化第 2 族金属 (Be-Ba) 的大体积对三联苯双(苯胺)配合物中的金属-芳烃相互作用:低氧化态碱土金属体系的潜在前体。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:4.6
- 作者:
Dat T Nguyen;Christoph Helling;Matthew J Evans;Cameron Jones - 通讯作者:
Cameron Jones
N-Heterocyclic Germylenes Supported by Bulky Dianionic N,N-Chelating Ligands
大体积双阴离子 N,N-螯合配体支持的 N-杂环甲锗烷基
- DOI:
10.1016/j.jorganchem.2024.123143 - 发表时间:
2024 - 期刊:
- 影响因子:2.3
- 作者:
Dat T Nguyen;Matthew J Evans;Cameron Jones - 通讯作者:
Cameron Jones
Matthew J Evans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('Matthew J Evans', 18)}}的其他基金
Zika virus nonstructural protein 5 inhibition of interferon signaling
寨卡病毒非结构蛋白 5 对干扰素信号传导的抑制
- 批准号:
10641222 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Deep mutational scanning of the Zika virus NS5 protein
寨卡病毒 NS5 蛋白的深度突变扫描
- 批准号:
10171769 - 财政年份:2020
- 资助金额:
$ 24.9万 - 项目类别:
Deep mutational scanning of the Zika virus NS5 protein
寨卡病毒 NS5 蛋白的深度突变扫描
- 批准号:
10057677 - 财政年份:2020
- 资助金额:
$ 24.9万 - 项目类别:
Host and viral determinants of hepatitis C virus macaque infection
丙型肝炎病毒猕猴感染的宿主和病毒决定因素
- 批准号:
8914166 - 财政年份:2015
- 资助金额:
$ 24.9万 - 项目类别:
Host and viral determinants of hepatitis C virus macaque infection
丙型肝炎病毒猕猴感染的宿主和病毒决定因素
- 批准号:
9012008 - 财政年份:2015
- 资助金额:
$ 24.9万 - 项目类别:
Hepatitis C virus polarized cell entry pathways
丙型肝炎病毒极化细胞进入途径
- 批准号:
8523846 - 财政年份:2012
- 资助金额:
$ 24.9万 - 项目类别:
Hepatitis C virus polarized cell entry pathways
丙型肝炎病毒极化细胞进入途径
- 批准号:
8396182 - 财政年份:2012
- 资助金额:
$ 24.9万 - 项目类别:
Occludin-specific HCV cell entry mechanisms
Occludin 特异性 HCV 细胞进入机制
- 批准号:
8337067 - 财政年份:2011
- 资助金额:
$ 24.9万 - 项目类别:
Studies of hepatitis C virus polarized cell entry and host factor requirements
丙型肝炎病毒极化细胞进入和宿主因子要求的研究
- 批准号:
7448969 - 财政年份:2008
- 资助金额:
$ 24.9万 - 项目类别:
相似海外基金
Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
- 批准号:
495434 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
- 批准号:
10586596 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
- 批准号:
10590479 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
- 批准号:
10642519 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
- 批准号:
23K06011 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
- 批准号:
10682117 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
- 批准号:
10708517 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
- 批准号:
10575566 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
- 批准号:
23K15696 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
- 批准号:
23K15867 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Grant-in-Aid for Early-Career Scientists