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Modeling the intracellular dynamics for Vif-APO mediated HIV-1.virus infection

Chinese Science Bulletin 2010年第22期55卷 2329-2340页

作者： wang yi1.2 & lai luhua1.3 1.center for theoretical biology,{1., Beijing 1.0871. china 2 School of Physics,{1., Beijing 1.0871. china 3 BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering,{1., Beijing 1.0871. china center for {1. biology Peking University Beijing 100871 China School of Physics Peking University Beijing 100871 China BNLMS State Key Laboratory for Structural Chemistry of Unstable and Stable Species College of Chemistry and Molecular Engineering Peking University Beijing 100871 China

The viral infectivity factor (Vif) was found to be essential for controlling HIV-1.virus infectivity. It targets cellular antiviral proteins in APOBEC family (APO) to trigger its fast degradation and inhibits APO packaging into nascent virion. In the present study, we propose a mathematical model to quantitatively study the intracellular dynamics of these typical virus-host interactions. Four sets of published experimental data were compared with simulation results to justify the model. Systematic parameter sensitivity and perturbation analysis showed that parameters related to APO are crucial to the infectivity of newly synthesized HIV-1.virus. Interestingly, we discovered that the synthesis rate of the viral structure protein Gag and the required number per nascent virion are optimized to achieve high virion production with minimal level of packaged APO, and large portion of model parameters are beneficial to virus only within a relatively small range. Furthermore, minor variations in several parameters related to viral protein Tat, the activator of viral RNA synthesis, were found to induce switch-like behaviors on both incorporated Vif and APO. These findings may provide new insights for understanding the high mutation rate of HIV-1.virus and its latency, as well as help identify key targets for therapeutic design.

关键词：病毒感染载脂蛋白 HIV 细胞内动力学抗病毒蛋白建模介导

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