论文标题

调节HIV潜伏期和激活的动态机制的定量分析

A Quantitative Analysis of Dynamic Mechanisms Regulating HIV Latency and Activation

论文作者

Xiong, Ruiqi, Su, Yang, Ao, Ping

论文摘要

目的:人类免疫缺陷病毒(HIV)的储藏量是潜在感染的细胞,是根除获得的免疫缺陷综合征(AIDS)的主要障碍。由于有机体中的嘈杂环境和多个影响因素,当前的动力学模型无法对HIV潜伏期的分子机制产生共同的理解。在这项工作中,通过新的动态结构分解,方程的确定性部分可以与随机噪声分开。因此,对普通微分方程的定点分析足以获得系统的不同稳态。方法:我们通过使用连续的随机微分方程建立了HIV转录过程的动态模型,该方程简化了描述系统所需的方程式的尺寸并增加了模型的可探索空间。潜在的函数和概率分布功能可以直观地表示病毒及其关系之间的不同状态及其关系。结果:基于我们的模型,定量分析了不同动力学参数对稳定性的影响,分别获得了BISSABLE和单一稳定状态系统的参数范围。通过将不同因素对动态分叉的影响与生物学实验的结果进行比较,可以验证这项工作的理论基础。结论:本文超越了以前的离散随机方法,可以定量分析通过普通微分方程的HIV转录调控的动态机制,这有助于促进以应对高维情况,并进一步研究VIV辅助工具的发生和发展,以指导实验和寻找临床治疗的设计。

Objective: The reservoir of human immunodeficiency virus (HIV) latently infected cells is the major obstacle for eradication of acquired immunodeficiency syndrome (AIDS). Due to the noisy environment and multiple influencing factors in the organism, current dynamical models cannot reach a common understanding of the molecular mechanism of HIV latency. In this work, through a new dynamical structure decomposition, the deterministic part of the equation can be separated from the stochastic noise. Thus, the fixed-point analysis of ordinary differential equation is enough to obtain the different steady states of the system. Methods: We established a dynamical model of HIV transcription process by using continuous stochastic differential equations, which simplifies the dimensions of equations needed to describe the system and increases the explorable space of the model. Different states between latency and activation of virus and their relations can be intuitively represented by potential functions and probability distribution functions. Results: Based on our model, the influence of different dynamical parameters on stability is quantitatively analyzed, the parameter ranges of the system in bistable and monostable states are obtained respectively. The theoretical basis of this work is verified by comparing the effects of different factors on dynamic bifurcation with the results of biological experiments. Conclusion: This paper goes beyond previous discrete stochastic methods, and can quantitatively analyze the dynamic mechanism of HIV transcriptional regulation through ordinary differential equations, which is beneficial to the promotion to deal with the high-dimensional situation, and further study the occurrence and development of AIDS in vivo, so as to guide the design of experiments and search for clinical treatment.

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