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Contribution of IL-32 gene expression to viral persistence

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:
10177863
负责人:
CRAIG E. CAMERON
金额:
$18.95万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-06-03 至 2023-05-31

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中文摘要
翻译
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。
英文摘要
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.
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DOI: 10.1016/j.bioactmat.2022.01.046
发表时间: 2022-08
期刊: Bioactive materials
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
Enteroviral 2C protein as a therapeutic target
Enteroviral 2C protein as a therapeutic target
Core C: Enzymology Core
Optimizing nucleoside analog efficacy with novel exonuclease inhibitors
  • 批准号:
    10514274
  • 项目类别:
  • 资助金额:
    $627.12万
  • 财政年份:
    2022
  • 负责人:
    CRAIG E. CAMERON
  • 依托单位:
海外基金