hiv感染的正常淋巴细胞的细胞周期动力学失调。

David M Asmuth, Nan Wang, Ying Lu, Xiao-Dong Li, Lisa Reece, Nicholas H A Terry, Richard B Pollard, Mostafa Nokta, James F Leary, R Allen White
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引用次数: 4

摘要

背景:病毒改变细胞基因转录和蛋白质结合的许多步骤对细胞周期调控至关重要,以优化生产感染的环境。考虑到病毒与宿主细胞的相互作用会导致细胞周期动力学的扰动,对感染人类免疫缺陷病毒(HIV)的正常T淋巴细胞的细胞周期阶段的持续时间进行了测量。方法:流式细胞术在细胞周期的多个时间点测量溴脱氧尿嘧啶标记和DNA含量染色的细胞,可以估计每个相的细胞比例,潜在的倍增时间,S期和G(2)/M期的持续时间。根据细胞内抗HIV核心p24抗体标记,对感染培养物中的HIV(+)和HIV(-)群体进行单独分析。一个新的数学模型,其中考虑细胞损失,开发估计细胞周期阶段。结果:(a)与对照组相比,HIV-1(SF2)感染细胞的S期延长。(b) S期的延迟是由于不表达HIV-1抗原的细胞群体(p24阴性)的延迟。(c)在hiv -1感染的培养物中证实了G(2)/M期细胞的积累,并且通过p24荧光强度测量与感染水平成正比。然而,所有模拟和hiv -1感染人群预测继续进行细胞分裂表现出相似的G(2)/ m期持续时间。(c)在受感染的培养中,潜在加倍时间较长;相比之下,p24(+)亚群解释了这种延迟。这表明该细胞群在G(0)/G(1)期存在孤立的延迟。结论:在体外模型中,HIV-1(SF2)感染可影响宿主细胞周期的多个阶段,提示新的HIV-1发病机制。HIV-1感染/p24(+)亚群中s期持续时间的延长和G(0)/G(1)期持续时间的延长需要进一步研究以确定机制途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cell cycle kinetic dysregulation in HIV-infected normal lymphocytes.

Background: Viruses alter cellular gene transcription and protein binding at many steps critical for cell cycle regulation to optimize the milieu for productive infection. Reasoning that virus-host cell interactions would result in perturbations of cell cycle kinetics, measurement of the duration of the phases of the cell cycle in normal T lymphocytes infected with human immunodeficiency virus (HIV) was undertaken.

Methods: Flow cytometric measurement of bromodeoxyuridine-labeled and DNA content-stained cells at multiple points through the cell cycle allowed estimation of the fraction of cells in each phase, the potential doubling-time, and the durations of S and G(2)/M phases. Separate analysis of the HIV(+) and HIV(-) populations within the infected cultures was performed based on intracellular, anti-HIV core p24 antibody labeling. A novel mathematical model, which accounted for cell loss, was developed to estimate cell cycle phases.

Results: (a) S phase was prolonged in the HIV-1(SF2)-infected cells compared with control. (b) This delay in S phase was due to delay in the population of cells not expressing HIV-1 antigens (p24 negative). (c) Accumulation of cells in G(2)/M phase was confirmed in HIV-1-infected cultures and was proportional to the level of infection as measured by p24 fluorescent intensity. However, all mock and HIV-1-infected populations predicted to proceed through cell division demonstrated similar G(2)/M-phase durations. (c) Potential doubling times were longer in the infected cultures; in contrast, the p24(+) subpopulations accounted for this delay. This suggests an isolated delay in the G(0)/G(1) phase for that population of cells.

Conclusions: Multiple phases of host cell cycle durations were affected by HIV-1(SF2) infection in this in vitro model, suggesting novel HIV-1 pathogenesis mechanisms. Prolonged S-phase durations in HIV-1 infected/p24(-) and G(0)/G(1)-phase durations in HIV-1 infected/p24(+) subpopulations require further study to identify mechanistic pathways.

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