Using herpes simplex virus as a tool to interrogate fundamental cellular stress pathways.
使用单纯疱疹病毒作为研究基本细胞应激途径的工具。
基本信息
- 批准号:RGPIN-2015-05039
- 负责人:
- 金额:$ 2.77万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2015
- 资助国家:加拿大
- 起止时间:2015-01-01 至 2016-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Studies of how viruses interact with host cells have led to the discovery of many conserved host processes. Indeed, viruses such as Herpes simplex virus (HSV) have co-evolved with humans for thousands of years, thus HSV is an excellent tool to study host functions. An emerging new paradigm, based in part on our contributions, is that cells recognize viral infection as a disruption of cellular homeostasis. Thus, the long-term program vision is to use HSV as a tool to elucidate fundamental aspects of how cells recognize and respond to stress at the molecular level. In a recent screen, we uncovered a novel interaction between the immediate early HSV protein ICP0 and the cellular protein G3BP2. ICP0 is a multifunctional protein that enables virus replication in part by subverting host intrinsic and innate responses. G3BP2 is an essential component of RNA stress granules (SGs), which form upon sensing of cellular stress and which have been associated with a variety of diseases. Recent studies indicate that many viruses either exploit or block SG formation, indicating that SGs play an important role in recognizing and mediating the outcome of a virus infection. Our preliminary studies suggest that ICP0 functions early during infection to block the formation of SGs, as efficient SGs formation is only visible following infection of HSV lacking ICP0 expression. The objectives of this proposal are to use our expertise in molecular virology, molecular biology and virus-host interactions to investigate the early events of HSV infection that trigger SG formation and to determine how SGs, and in particular G3BP2, modulate virus infection. We will also evaluate the importance of the interaction between ICP0 and G3BP2 on SG-dependent and SG-independent functions of G3BP2. Using resources, techniques and infrastructure that are well-established and available within my laboratory, these studies will enhance our understanding of basic cellular processes, such as induction of effective cell stress responses upon disruption of homeostasis. As these responses underlie the success of an organism as a whole, the generation of such fundamental knowledge will lead to a greater understanding of the basic mechamisms underlying many diseases.
对病毒如何与宿主细胞相互作用的研究已经发现了许多保守的宿主过程。事实上,单纯疱疹病毒(HSV)等病毒已经与人类共同进化了数千年,因此HSV是研究宿主功能的绝佳工具。一个新兴的新范式,部分基于我们的贡献,是细胞将病毒感染识别为细胞稳态的破坏。因此,长期计划的愿景是使用HSV作为工具来阐明细胞如何在分子水平上识别和响应应激的基本方面。在最近的筛选中,我们发现了直接早期HSV蛋白ICP0和细胞蛋白G3BP2之间的一种新的相互作用。ICP0是一种多功能蛋白,部分通过破坏宿主的内在和先天反应来实现病毒复制。G3BP2是RNA应激颗粒(SGs)的重要组成部分,SGs是在感知细胞应激时形成的,与多种疾病有关。最近的研究表明,许多病毒利用或阻断了SG的形成,这表明SGs在识别和介导病毒感染的结果中起着重要作用。我们的初步研究表明,ICP0在感染早期起作用,阻止SGs的形成,因为只有在感染缺乏ICP0表达的HSV后才能看到有效的SGs形成。该提案的目的是利用我们在分子病毒学、分子生物学和病毒-宿主相互作用方面的专业知识,研究HSV感染早期触发SG形成的事件,并确定SGs,特别是G3BP2如何调节病毒感染。我们还将评估ICP0和G3BP2之间的相互作用对G3BP2的sg依赖和sg独立功能的重要性。利用我的实验室已经建立和可用的资源、技术和基础设施,这些研究将增强我们对基本细胞过程的理解,例如在破坏体内平衡时诱导有效的细胞应激反应。由于这些反应是整个生物体成功的基础,这些基础知识的产生将导致对许多疾病的基本机制有更深入的了解。
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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Mossman, Karen其他文献
Two DNA vaccines protect against severe disease and pathology due to SARS-CoV-2 in Syrian hamsters.
- DOI:
10.1038/s41541-022-00461-5 - 发表时间:
2022-04-26 - 期刊:
- 影响因子:9.2
- 作者:
Babuadze, George Giorgi;Fausther-Bovendo, Hugues;deLaVega, Marc-Antoine;Lillie, Brandon;Naghibosadat, Maedeh;Shahhosseini, Nariman;Joyce, Michael A.;Saffran, Holly A.;Lorne Tyrrell, D.;Falzarano, Darryl;Senthilkumaran, Chandrika;Christie-Holmes, Natasha;Ahn, Steven;Gray-Owen, Scott D.;Banerjee, Arinjay;Mubareka, Samira;Mossman, Karen;Dupont, Chanel;Pedersen, Jannie;Lafrance, Mark-Alexandre;Kobinger, Gary P.;Kozak, Robert - 通讯作者:
Kozak, Robert
Handling of the Cotton Rat in Studies for the Pre-clinical Evaluation of Oncolytic Viruses
- DOI:
10.3791/52232 - 发表时间:
2014-11-01 - 期刊:
- 影响因子:1.2
- 作者:
Cuddington, Breanne;Verschoor, Meghan;Mossman, Karen - 通讯作者:
Mossman, Karen
Seroprevalence in Bats and Detection of Borrelia burgdorferi in Bat Ectoparasites
- DOI:
10.3390/microorganisms8030440 - 发表时间:
2020-03-01 - 期刊:
- 影响因子:4.5
- 作者:
Banerjee, Arinjay;Baid, Kaushal;Mossman, Karen - 通讯作者:
Mossman, Karen
Sensitivity to Neutralizing Antibodies and Resistance to Type I Interferons in SARS-CoV-2 R.1 Lineage Variants, Canada.
- DOI:
10.3201/eid2907.230198 - 发表时间:
2023-07 - 期刊:
- 影响因子:11.8
- 作者:
Jacob, Rajesh Abraham;Zhang, Ali;Ajoge, Hannah O.;D'Agostino, Michael R.;Nirmalarajah, Kuganya;Shigayeva, Altynay;Demian, Wael L.;Baker, Sheridan J. C.;Derakhshani, Hooman;Rossi, Laura;Nasir, Jalees A.;Panousis, Emily M.;Draia, Ahmed N.;Vermeiren, Christie;Gilchrist, Jodi;Smieja, Nicole;Bulir, David;Smieja, Marek;Surette, Michael G.;McArthur, Andrew G.;McGeer, Allison J.;Mubareka, Samira;Banerjee, Arinjay;Miller, Matthew S.;Mossman, Karen - 通讯作者:
Mossman, Karen
Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection
- DOI:
10.1016/j.isci.2020.100958 - 发表时间:
2020-03-27 - 期刊:
- 影响因子:5.8
- 作者:
Banerjee, Arinjay;Zhang, Xi;Mossman, Karen - 通讯作者:
Mossman, Karen
Mossman, Karen的其他文献
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{{ truncateString('Mossman, Karen', 18)}}的其他基金
McMaster University Application to EDI Stipend
麦克马斯特大学 EDI 津贴申请
- 批准号:
CRCES-2022-00025 - 财政年份:2022
- 资助金额:
$ 2.77万 - 项目类别:
Canada Research Chair EDI Stipend
Wild-caught bats as a model to understand the evolution of virus-host interactions
野生捕获的蝙蝠作为了解病毒与宿主相互作用进化的模型
- 批准号:
RGPIN-2018-05426 - 财政年份:2022
- 资助金额:
$ 2.77万 - 项目类别:
Discovery Grants Program - Individual
Wild-caught bats as a model to understand the evolution of virus-host interactions
野生捕获的蝙蝠作为了解病毒与宿主相互作用进化的模型
- 批准号:
RGPIN-2018-05426 - 财政年份:2021
- 资助金额:
$ 2.77万 - 项目类别:
Discovery Grants Program - Individual
Crces-2021-1
CCES-2021-1
- 批准号:
CRCES-2021-00019 - 财政年份:2021
- 资助金额:
$ 2.77万 - 项目类别:
Canada Research Chair EDI Stipend
3D fluorescence microscope for virus-host interaction studies
用于病毒-宿主相互作用研究的 3D 荧光显微镜
- 批准号:
RTI-2022-00621 - 财政年份:2021
- 资助金额:
$ 2.77万 - 项目类别:
Research Tools and Instruments
Wild-caught bats as a model to understand the evolution of virus-host interactions
野生捕获的蝙蝠作为了解病毒与宿主相互作用进化的模型
- 批准号:
RGPIN-2018-05426 - 财政年份:2020
- 资助金额:
$ 2.77万 - 项目类别:
Discovery Grants Program - Individual
Wild-caught bats as a model to understand the evolution of virus-host interactions
野生捕获的蝙蝠作为了解病毒与宿主相互作用进化的模型
- 批准号:
RGPIN-2018-05426 - 财政年份:2019
- 资助金额:
$ 2.77万 - 项目类别:
Discovery Grants Program - Individual
Wild-caught bats as a model to understand the evolution of virus-host interactions
野生捕获的蝙蝠作为了解病毒与宿主相互作用进化的模型
- 批准号:
RGPIN-2018-05426 - 财政年份:2018
- 资助金额:
$ 2.77万 - 项目类别:
Discovery Grants Program - Individual
Elucidating the mechanism of action of Mirexus Biotechnologies Inc.'s immunomodulatory phytoglyogen (IM-PhG) in increasing virus vector production
阐明 Mirexus Biotechnologies Inc. 的免疫调节植物糖原 (IM-PhG) 在增加病毒载体产量方面的作用机制
- 批准号:
523780-2018 - 财政年份:2018
- 资助金额:
$ 2.77万 - 项目类别:
Engage Grants Program
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