Membrane Hijacking: Biogenesis and Fate of Enveloped Hepatovirus
膜劫持:包膜肝病毒的生物发生和命运
基本信息
- 批准号:8549949
- 负责人:
- 金额:$ 35.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-24 至 2017-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcuteAcute HepatitisAddressAntibodiesAutophagocytosisAutophagosomeBile fluidBiogenesisBiological AssayBloodC-terminalCapsidCapsid ProteinsCell Culture TechniquesCell membraneCell physiologyCellsComplexDataDetergentsDevelopmentDiseaseElementsEventFamilyFamily PicornaviridaeGenomeGoalsGrowthHepatitis AHepatitis A VaccinesHepatitis A VirusHepatovirusHumanImmunoelectron MicroscopyImmunoglobulinsIn VitroInfectionInterferonsLiverMediatingMembraneModelingMolecular GeneticsMultivesicular BodyMusOralPan GenusPathogenesisPathway interactionsPlayPrimary carcinoma of the liver cellsProcessProductionProphylactic treatmentProteinsProteomicsRNA InterferenceRNA VirusesResistanceResolutionRoleSerumSignal TransductionSorting - Cell MovementStructural ModelsStructureStudy modelsVaccinesViralViral hepatitisVirionVirusVirus Diseasesanti-hepatitis Abasehepatitis A virus antibodiesinsightmemberneonatal Fc receptorneutralizing antibodynonhuman primatenovelparticlepathogenpolarized cellpolypeptideprotective effectprotein expressionpublic health relevanceviral resistancevirus pathogenesis
项目摘要
DESCRIPTION (provided by applicant): The Picornaviridae are a large and diverse family of positive-strand RNA viruses that include a number of important human pathogens, among them hepatitis A virus (HAV), an hepatotropic virus that is the causative agent of acute hepatitis A and
the only species in the genus Hepatovirus. As a family, picornaviruses are non-enveloped. Their genomes are encapsidated within icosahedral capsids comprised of 60 copies of each of 3-4 polypeptides. High-resolution structural models have been developed for several pathogenic picornaviruses but not HAV, and its structure remains poorly defined. We have discovered that most HAV particles released by cultured human hepatoma (Huh-7.5) cells are fully enveloped in host-derived membranes. Remarkably, biophysical studies indicate that these enveloped hepatoviruses (eHAV) are also the dominant form of virus circulating in the blood during acute hepatitis A. eHAV particles are fully infectious, yet highly resistant to neutralizing anti-HAV antibodies. These novel observations provide a new view of hepatitis A pathogenesis, and raise important questions about the mechanism by which vaccines provide protection against hepatitis A even when administered 2 weeks after infection. Specific Aim 1 will use quantitative proteomics and immunoelectron microscopy to characterize viral and host-derived proteins present in eHAV particles, as these may provide clues to the origin of eHAV. Specific Aim 2 focuses directly on the biogenesis of eHAV, and will use reverse molecular genetics and RNAi knockdown of multiple host proteins to probe interactions of HAV with ESCRT complexes involved in endosomal sorting and proteins involved in autophagy. Both cellular processes are potentially relevant to eHAV release from cells. Specific Aim 3 addresses the fate of eHAV, focusing particularly on how anti-HAV antibodies neutralize eHAV after its entry into permissive cells, a process that is likely to account for the protection vaccines afford against disease when administered after infection with the virus. A subsidiary aim is to develop a murine model of hepatitis A in which these events can be studied and which can replace existing nonhuman primate models of HAV infection. Although a completely novel finding, "membrane hijacking" may not be unique to HAV. These studies are thus broadly relevant to other non-enveloped viruses and how vaccine-induced antibodies provide protection against disease.
描述(由申请人提供):小核糖核酸病毒科是一个庞大而多样的正链RNA病毒家族,包括许多重要的人类病原体,其中包括甲型肝炎病毒(HAV),一种嗜肝病毒,是急性甲型肝炎和乙型肝炎的病原体
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)
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Stanley M. Lemon其他文献
Hepatitis Viruses
- DOI:
10.1007/978-1-4615-0881-6 - 发表时间:
2002 - 期刊:
- 影响因子:0
- 作者:
Stanley M. Lemon - 通讯作者:
Stanley M. Lemon
A simple method for clonal selection of hepatitis A virus based on recovery of virus from radioimmunofocus overlays.
一种基于从放射免疫聚焦覆盖物中回收病毒的甲型肝炎病毒克隆选择的简单方法。
- DOI:
10.1016/0166-0934(85)90040-0 - 发表时间:
1985 - 期刊:
- 影响因子:3.1
- 作者:
Stanley M. Lemon;Robert W. Jansen - 通讯作者:
Robert W. Jansen
Ins and outs of picornaviruses
小 RNA 病毒的来龙去脉
- DOI:
10.1038/nature21116 - 发表时间:
2017-01-11 - 期刊:
- 影响因子:48.500
- 作者:
Kevin L. McKnight;Stanley M. Lemon - 通讯作者:
Stanley M. Lemon
7. mRNA for selenoprotein P, a hepatokine, binds RIG-I protein and inhibits the RIG-I-mediated type I interferon response
7. 硒蛋白 P(一种肝因子)的 mRNA 结合 RIG-I 蛋白并抑制 RIG-I 介导的 I 型干扰素反应
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:0
- 作者:
Kazuhisa Murai;Masao Honda;Tetsuro Shimakami;Takayoshi Shirasaki;Hirofumi Misu;Toshinari Takamura;Stanley M. Lemon;Seishi Murakami;Shuichi Kaneko - 通讯作者:
Shuichi Kaneko
Integrin beta 1 facilitates non-enveloped hepatitis E virus cell entry through the recycling endosome
整合素β1通过回收内体促进非包膜戊型肝炎病毒进入细胞
- DOI:
10.1038/s41467-025-61071-y - 发表时间:
2025-06-26 - 期刊:
- 影响因子:15.700
- 作者:
Rebecca Fu;Paula Jordan;Zoe Engels;Jasmin Alara Weihs;Josias Mürle;Huanting Chi;Sebastian Burbano de Lara;Barbara Helm;Mara Klöhn;Jungen Hu;Andrew Freistaedter;Tobias Boettler;Marco Binder;Ursula Klingmüller;Eike Steinmann;Pierre-Yves Lozach;Thibault Tubiana;Stanley M. Lemon;Viet Loan Dao Thi - 通讯作者:
Viet Loan Dao Thi
Stanley M. Lemon的其他文献
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{{ truncateString('Stanley M. Lemon', 18)}}的其他基金
Critical Lipid Species in the Hepatovirus Lifecycle
肝病毒生命周期中的关键脂质种类
- 批准号:
10306348 - 财政年份:2019
- 资助金额:
$ 35.72万 - 项目类别:
Critical Lipid Species in the Hepatovirus Lifecycle
肝病毒生命周期中的关键脂质种类
- 批准号:
10530593 - 财政年份:2019
- 资助金额:
$ 35.72万 - 项目类别:
Critical Lipid Species in the Hepatovirus Lifecycle
肝病毒生命周期中的关键脂质种类
- 批准号:
9913862 - 财政年份:2019
- 资助金额:
$ 35.72万 - 项目类别:
Novel Pathogen Recognition Pathways and Control of Hepatitis A Virus
新的病原体识别途径和甲型肝炎病毒的控制
- 批准号:
9233911 - 财政年份:2014
- 资助金额:
$ 35.72万 - 项目类别:
Membrane Hijacking: Biogenesis and Fate of Quasi-Enveloped Hepatovirus
膜劫持:准包膜肝病毒的生物发生和命运
- 批准号:
9764230 - 财政年份:2012
- 资助金额:
$ 35.72万 - 项目类别:
Murine Model of HCV-Associated Human Liver Cancer
HCV 相关人类肝癌的小鼠模型
- 批准号:
8625280 - 财政年份:2012
- 资助金额:
$ 35.72万 - 项目类别:
Membrane Hijacking: Biogenesis and Fate of Enveloped Hepatovirus
膜劫持:包膜肝病毒的生物发生和命运
- 批准号:
8420039 - 财政年份:2012
- 资助金额:
$ 35.72万 - 项目类别:
Murine Model of HCV-Associated Human Liver Cancer
HCV 相关人类肝癌小鼠模型
- 批准号:
8219397 - 财政年份:2012
- 资助金额:
$ 35.72万 - 项目类别:
Murine Model of HCV-Associated Human Liver Cancer
HCV 相关人类肝癌小鼠模型
- 批准号:
8464678 - 财政年份:2012
- 资助金额:
$ 35.72万 - 项目类别:
Membrane Hijacking: Biogenesis and Fate of Quasi-Enveloped Hepatovirus
膜劫持:准包膜肝病毒的生物发生和命运
- 批准号:
10223138 - 财政年份:2012
- 资助金额:
$ 35.72万 - 项目类别:
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