The effects of cells that survive direct influenza A virus infection on lung repair
直接甲型流感病毒感染后存活的细胞对肺修复的影响
基本信息
- 批准号:9372505
- 负责人:
- 金额:$ 19.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-06-15 至 2019-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdaptive Immune SystemAlveolarBehaviorBiological AssayCell Culture TechniquesCell DeathCell Differentiation processCell ProliferationCell SurvivalCellsCessation of lifeCoculture TechniquesDataDistalEnterobacteria phage P1 Cre recombinaseEpithelialEpithelial CellsEpitheliumErythrocytesGenerationsGenetic TranscriptionGoalsGrowthIn VitroInfectionInflammatoryInfluenzaInfluenza A Virus, H1N1 SubtypeInfluenza A virusInfluenza B VirusInjuryKnowledgeLabelLeadLungMediatingModelingMusNatural regenerationOrganoidsPhenotypePlayPopulationProcessPuerto RicoReporterResolutionRoleSeveritiesSpecificityStem cellsSurvival RateSurvivorsTestingTherapeuticTranscriptTransgenic OrganismsViralVirusVirus DiseasesWorkalveolar epitheliumcell behaviorcell typecytokinedesigndifferential expressionexperimental studyin vivoinfluenza virus straininfluenzaviruslung regenerationlung repairnovelnovel therapeuticsrepairedrespiratorytherapy developmenttranscriptome sequencing
项目摘要
Project Summary/Abstract
Influenza A virus (IAV) is an acute, cytopathic virus that infects a range of different cell types, but principally
lung epithelial cells. Viral infection causes extensive damage to both the proximal and alveolar airways.
Because virus growth is highly cytolytic in cell culture, and the virus is completely eliminated from the host by
the adaptive immune system, it has long been believed that no infected cells are able to survive direct IAV
infection. A derivative of this assumption is that the virus is incapable of influencing the host after the
resolution of viral infection.
I recently developed a Cre recombinase-expressing IAV, which allowed me to permanently label every infected
cell and follow their fates. With this virus and transgenic reporter mouse lines, I identified a population of
epithelial club cells that survived direct and productive viral infection. Not only can these cells eliminate all
traces of the virus and survive, but further characterization of these cells revealed that the cells acquire an
altered, and generally inflammatory, transcriptional profile after surviving. Specific depletion of these cells
enhanced epithelial regeneration, indicating that survivor cells delay lung repair after the resolution of viral
infection.
The implication of my preliminary data is that IAV infection leads to the generation of a population of
transcriptionally reprogrammed survivor cells that have important inhibitory roles in lung repair. To the best of
my knowledge, the contribution of survivor cell populations to lung repair has never been studied. In this
proposal, I will assay how the strain specificity of IAV influences the numbers of surviving club cells in vivo. I
will then define how survivor cells influence uninfected basal/progenitor cell behavior as well as track the fates
of survivor club cells during lung repair. I will specifically evaluate the effects of surviving club cells on the
repair of both the larger and alveolar epithelium. The proposed work will explore a completely unstudied
regulator of lung repair, and may identify novel mechanisms to therapeutically enhance epithelial regeneration
after viral infections.
项目总结/摘要
甲型流感病毒(IAV)是一种急性细胞病变病毒,感染一系列不同的细胞类型,但主要是
肺上皮细胞病毒感染引起近端和肺泡气道的广泛损伤。
因为病毒生长在细胞培养物中是高度溶细胞的,并且病毒通过细胞培养物从宿主中完全消除。
适应性免疫系统,长期以来一直认为,没有感染的细胞能够生存直接IAV
感染这种假设的一个衍生物是,病毒在感染后不能影响宿主。
解决病毒感染。
我最近开发了一种表达Cre重组酶的IAV,
细胞,并遵循他们的命运。用这种病毒和转基因报告小鼠品系,我鉴定了一个
上皮棒状细胞在直接和生产性病毒感染中存活。这些细胞不仅可以消除所有
病毒的痕迹,并存活下来,但进一步表征这些细胞显示,细胞获得了一个
存活后的转录谱发生改变,通常是炎症性的。这些细胞的特异性耗竭
增强的上皮再生,表明存活细胞延迟了病毒感染后的肺修复。
感染
我的初步数据的含义是,IAV感染导致了一个群体的产生,
转录重编程的幸存细胞在肺修复中具有重要的抑制作用。尽最大
据我所知,幸存细胞群对肺修复的贡献从未被研究过。在这
在本研究中,我将分析IAV的株系特异性如何影响活的俱乐部细胞的数量。我
然后将确定存活细胞如何影响未感染的基底/祖细胞行为,并跟踪其命运。
幸存者俱乐部细胞的数量我将专门评估存活的俱乐部细胞对
修复较大和肺泡上皮。这项拟议中的工作将探索一个完全未经研究的
肺修复的调节因子,并可能确定治疗增强上皮再生的新机制
病毒感染后。
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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Nicholas S Heaton其他文献
Nicholas S Heaton的其他文献
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{{ truncateString('Nicholas S Heaton', 18)}}的其他基金
Control of influenza virus induced type I interferon signaling during pregnancy
妊娠期间流感病毒诱导的 I 型干扰素信号传导的控制
- 批准号:
10584008 - 财政年份:2022
- 资助金额:
$ 19.56万 - 项目类别:
The pathogenic effects of epithelial cells surviving direct influenza virus infection
流感病毒直接感染后存活的上皮细胞的致病作用
- 批准号:
10331745 - 财政年份:2019
- 资助金额:
$ 19.56万 - 项目类别:
Loss of cellular identity after influenza virus infection and effects on pulmonary function
流感病毒感染后细胞特性的丧失及其对肺功能的影响
- 批准号:
10213821 - 财政年份:2018
- 资助金额:
$ 19.56万 - 项目类别:
Loss of cellular identity after influenza virus infection and effects on pulmonary function
流感病毒感染后细胞特性的丧失及其对肺功能的影响
- 批准号:
10438638 - 财政年份:2018
- 资助金额:
$ 19.56万 - 项目类别:
Survival of influenza A virus infected cells and effects on pathogenesis
甲型流感病毒感染细胞的存活及其对发病机制的影响
- 批准号:
9188524 - 财政年份:2015
- 资助金额:
$ 19.56万 - 项目类别:
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