论文标题
HIV潜伏期重新激活激活剂的噪声增强子的非平衡机制
The Nonequilibrium Mechanism of Noise Enhancer synergizing with Activator in HIV Latency Reactivation
论文作者
论文摘要
调节化学物质可以与转录激活剂在重新激活潜在的HIV以消除潜在的HIV储藏剂时协同作用。为了了解潜在的生物分子机制，我们研究了先前的两种状态模型，并确定了协同作用的两个必要条件：转录激活剂对噪声增强子的抑制作用的假设；并频繁地过渡到基因非转录 - 腐蚀状态。然后，我们开发了一个具有TAT转录/翻译的四个环境模型，发现药物协同作用主要取决于HIV启动子的遗传调节动力学的能量和方向。转录激活剂的抑制作用实际上是非平衡基因过渡系统中能量耗散的现象。总体而言，循环四州模型表明，能量耗散在艾滋病毒潜伏期重新激活中起着至关重要的作用，这可能对改善药物作用并识别慢跑病毒潜伏期重新激活的其他协同作用可能有用。
Noise-modulating chemicals can synergize with transcriptional activators in reactivating latent HIV to eliminate latent HIV reservoirs. To understand the underlying biomolecular mechanism, we investigate a previous two-gene-state model and identify two necessary conditions for the synergy: an assumption of inhibition effect of transcription activators on noise enhancers; and frequent transitions to the gene non-transcription-permissive state. We then develop a loop-four-gene-state model with Tat transcription/translation and find that drug synergy is mainly determined by the magnitude and direction of energy input into the genetic regulatory kinetics of the HIV promoter. The inhibition effect of transcription activators is actually a phenomenon of energy dissipation in the nonequilibrium gene transition system. Overall, the loop-four-state model demonstrates that energy dissipation plays a crucial role in HIV latency reactivation, which might be useful for improving drug effects and identifying other synergies on lentivirus latency reactivation.
