Contribution of IL-32 gene expression to viral persistence
IL-32 基因表达对病毒持久性的贡献
基本信息
- 批准号:10177863
- 负责人:
- 金额:$ 18.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-03 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffinityAntibodiesAntiviral AgentsAntiviral ResponseAvidityBiomedical EngineeringCardiac MyocytesCardiomyopathiesCell Culture TechniquesCell LineCell NucleusCellsChronicCollaborationsComplementary DNACoxsackie VirusesCoxsackievirus InfectionsCulture MediaCytolysisCytoplasmDevelopmentEpithelial CellsGene ExpressionGene Expression ProfilingGenesGenotypeGoalsGrantHela CellsHumanHuman poliovirusImmuneImmunityInfectionInflammationInnate Immune ResponseInterferon-alphaInterferon-betaInterferonsKnock-outKnowledgeMeasles virusMediator of activation proteinModelingMolecularNonlyticPathway interactionsPharmacologyPhenotypePopulationPredispositionProtein IsoformsProteomicsPublic HealthRNA VirusesRegimenSystemTherapeuticTimeToll-like receptorsUp-RegulationViralViral AntigensVirusVirus DiseasesVirus ReplicationWorkacute infectionbasechronic infectionexperimental studygene discoveryinduced pluripotent stem cellinhibitor/antagonistpathogenpersonalized medicineprogramsprophylacticresponsesensorsingle cell analysistranscriptome
项目摘要
Project Abstract
A case is being made for the utility of MeV persistence in development of lifelong immunity. The thought
is that persistent infection of epithelial cells, in addition to immune cells, may produce virus or viral
antigens to promote affinity maturation of antibodies for a sufficient duration of time that antibodies of
the highest avidity are produced. What governs establishment of a phenotype in an epithelial cell
conducive to establishment of a persistent infection is not known. However, such a cell should be able
to suppress but not eliminate virus multiplication, and virus release must occur by a non-lytic
mechanism to avoid a state of chronic inflammation. Establishing the existence of such persistent-
infection-competent epithelial cells and their gene expression, especially genes involved in control of
virus multiplication, is an essential first step in understanding the molecular basis of viral persistence.
Our single-cell analysis of poliovirus (PV) infection revealed a population of HeLa cells that were quite
proficient at supporting PV multiplication without lysis for as long as 36 h post-infection, which was the
duration of the experiment. We developed a strategy to isolate this sub-population of persistently-
infected cells using standard cell-culture approaches by adding an inhibitor of PV entry to the culture
media. We observed PV persistence for as long as six days post-infection, again the duration of the
experiment. Gene-expression analysis of these persistently-infected cells revealed a near-complete
suppression of sensors of viruses and other pathogens, including Toll-like receptors and “toll-free”
(cytosolic) receptors18. The gene for IL-32 was induced 7 fold (P-value <0.001). IL-32 has been
implicated in antiviral responses that are independent of type I and II interferons (IFNs); however,
effectors of the IL-32-dependent, antiviral pathway have yet to be discovered. The overarching goal of
the program that we will initiate under the auspices of this R21 grant is elucidation of genes, pathways,
and mechanisms required for viral persistence. The first goal of this application is to identify genes that
may contribute to establishment of persistence of CVB3 in human cardiomyocytes. The second goal of
this application is to inspire hypotheses for the mechanism of IL-32 action. These goals will be pursued
as indicated by the following aims: (1) Discover genes contributing to CVB3 persistence in human
cardiomyocytes; and (2) Discover effectors of the IL-32-dependent antiviral state in HeLa cells.
项目摘要
有证据表明,甲型肝炎病毒的持久性在终身免疫的发展中是有用的。我的想法
除了免疫细胞外,上皮细胞的持续感染还可能产生病毒或病毒
在足够长的时间内促进抗体亲和力成熟的抗原
产生最高的亲和力。是什么支配着上皮细胞表型的建立
是否有利于建立持续性感染尚不清楚。然而,这样的单元格应该能够
为了抑制但不是消除病毒的增殖,病毒的释放必须由非裂解剂发生
避免慢性炎症状态的机制。证明存在这种持久的-
侵染能力强的上皮细胞及其基因表达,特别是参与调控的基因
病毒增殖,是了解病毒持续存在的分子基础的重要第一步。
我们对脊髓灰质炎病毒(PV)感染的单细胞分析显示,HeLa细胞群相当于
擅长支持PV在感染后36小时内不裂解增殖,这是
实验的持续时间。我们制定了一种策略来隔离这群持续不断的-
使用标准的细胞培养方法,通过在培养中添加PV进入的抑制剂来感染细胞
媒体。我们在感染后观察了长达6天的PV持续性,再次观察了
做实验。对这些持续感染的细胞进行的基因表达分析显示,
抑制病毒和其他病原体的传感器,包括Toll样受体和“免费”
(细胞质)受体18.IL-32基因被诱导7倍(P<0.001)。IL-32已经被
与独立于I型和II型干扰素(IFN)的抗病毒反应有关;然而,
IL-32依赖的抗病毒途径的效应器尚未被发现。的首要目标是
我们将在这笔R21拨款的赞助下启动的计划是阐明基因、途径、
以及病毒持续存在所需的机制。这个应用程序的第一个目标是识别
可能与CVB3在人心肌细胞中持续存在有关。的第二个目标
这一应用旨在启发对IL-32作用机制的假说。我们将努力实现这些目标
主要目的如下:(1)发现与人类CVB3持续相关的基因
(2)在HeLa细胞中发现依赖IL-32的抗病毒状态的效应物。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Robust genome and RNA editing via CRISPR nucleases in PiggyBac systems.
- DOI:10.1016/j.bioactmat.2022.01.046
- 发表时间:2022-08
- 期刊:
- 影响因子:18.9
- 作者:Jiang Y;Hoenisch RC;Chang Y;Bao X;Cameron CE;Lian XL
- 通讯作者:Lian XL
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{{ truncateString('CRAIG E. CAMERON', 18)}}的其他基金
Enteroviral 2C protein as a therapeutic target
肠道病毒2C蛋白作为治疗靶点
- 批准号:
10609524 - 财政年份:2022
- 资助金额:
$ 18.95万 - 项目类别:
Enteroviral 2C protein as a therapeutic target
肠道病毒2C蛋白作为治疗靶点
- 批准号:
10450381 - 财政年份:2022
- 资助金额:
$ 18.95万 - 项目类别:
Optimizing nucleoside analog efficacy with novel exonuclease inhibitors
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10514274 - 财政年份:2022
- 资助金额:
$ 18.95万 - 项目类别:
Contribution of IL-32 gene expression to viral persistence
IL-32 基因表达对病毒持久性的贡献
- 批准号:
10057016 - 财政年份:2020
- 资助金额:
$ 18.95万 - 项目类别:
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