Intracellular transactivation of HIV can account for the decelerating decay of virus load during drug therapy
Intracellular transactivation of HIV can account for the decelerating decay of virus load during drug therapy
复制标题
DOI：
10.1038/msb.2010.4
复制
发表时间：
2010-02-01
影响因子：
9.9
通讯作者：
De Boer, Rob J.
中科院分区：
文献类型：
--
作者：
Althaus, Christian L.;De Boer, Rob J.
基本的病毒动力学模型对于理解HIV复制的定量问题至关重要。然而，病毒生命周期的几个部分仍然难以捉摸。最关键的步骤之一是病毒转录的开始，其由诱导正反馈环的调节蛋白转录反式激活因子（达特）控制。已经表明，这种反馈回路可以在两种状态之间交替，导致病毒转录的瞬时激活。使用Monte Carlo模拟，我们集成的反式激活电路到一个新的病毒动力学模型具有年龄依赖性的反式激活率和逆转成潜伏期。受感染细胞在活化和潜伏状态之间的循环导致治疗后病毒载量的典型减速衰减。此外，我们假设潜伏感染细胞的激活是由整合的前病毒的基础转录率而不是细胞内或细胞外环境决定的。最后，我们的系统方法来模拟病毒动力学提供了一个有前途的框架来推断细胞群体的细胞外动态从他们的细胞内反应网络。Molecular Systems Biology 6：348; 2010年2月16日在线发表; doi：10.1038/msb.2010.4
Basic virus dynamics models have been essential in understanding quantitative issues of HIV replication. However, several parts of the viral life cycle remain elusive. One of the most critical steps is the start of viral transcription, which is governed by the regulatory protein trans-activator of transcription ( Tat) that induces a positive feedback loop. It has been shown that this feedback loop can alternate between two states leading to a transient activation of viral transcription. Using Monte Carlo simulations, we integrate the transactivation circuit into a new virus dynamics model having an age-dependent transactivation rate and reversion into latency. The cycling of infected cells between an activated and latent state results in the typical decelerating decay of virus load following therapy. Further, we hypothesize that the activation of latently infected cells is governed by the basal transcription rate of the integrated provirus rather than the intra-or extracellular environment. Finally, our systems approach to modeling virus dynamics offers a promising framework to infer the extracellular dynamics of cell populations from their intracellular reaction networks. Molecular Systems Biology 6: 348; published online 16 February 2010; doi:10.1038/msb.2010.4