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病毒感染因子Vif对控制HIV-1病毒的感染能力非常重要,它通过和细胞抗病毒蛋白APOBEC家族(简写成APO)的相互作用,引发APO的快速降解从而阻止APO被包装到新生的病毒粒子中.在本论文中,我们提出一个数学模型来定量地描述这种典型的病毒-宿主相互作用.为检验该模型,我们将计算模拟结果和4组已发表的实验数据进行了对比.在此基础上进行了系统的参数敏感性分析和扰动分析,表明与APO相关的参数对于新生HIV-1病毒粒子的感染能力非常重要.我们发现病毒结构蛋白Gag的生成速率以及单位新生病毒粒子所需的Gag蛋白分子数目呈现出对高病毒粒子产生速率和低APO包装入新生病毒粒子程度的优化现象,并且模型中的许多参数只在较小的取值范围内对病毒才是有益的.我们还发现针对激活病毒RNA合成的调控蛋白Tat的小扰动会导致Vif和APO包装入新生病毒粒子的量呈现开关效应.这些发现将有助于理解HIV-1病毒的高突变率和潜伏现象,并为药物设计定位关键的靶标提供帮助.
Vif, a viral infectious agent, is very important in controlling the ability of the HIV-1 virus to infect, and by rapidly interacting with the APOBEC family of cellular antiviral proteins (abbreviated APO), trigger rapid APO degradation that prevents APO from being packaged into nascent virions In this paper, we present a mathematical model to quantitatively describe this typical virus-host interaction. To test this model, we compared the calculated results with four published sets of experimental data, based on which , A systematic parametric sensitivity analysis and perturbation analysis were performed showing that the APO-related parameters are important for the ability of the nascent HIV-1 virion to infect.We have found that the rate of formation of the viral structural protein Gag and the required Gag per unit virion The number of protein molecules exhibits an optimization of the rate of production of high virions and the low degree of APO encapsulation into virions, and many of the parameters in the model are beneficial to the virus only in small ranges. We also find that A small perturbation that activates the regulatory protein Tat that activates the synthesis of viral RNA can cause the amount of Vif and APO packaged into virion to exhibit a switching effect These findings should help to understand the high mutation rates and latency of the HIV-1 virus and help design the drug to target key targets.