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

作　　者：WANG Yi1,2 & LAI LuHua1,3 1 Center for Theoretical Biology, Peking University, Beijing 100871, China 2 School of Physics, Peking University, Beijing 100871, China 3 BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China 

出　　处：《Chinese Science Bulletin》2010年第22期2329-2340,共12页

基　　金：supported by the National Natural Science Foundation of China (10721403);National Basic Research Program of China (2009C-B918500);the National High-Technology Research & Development Program of China (2006AA020400)

摘　　要：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.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 

分 类 号：R512.91[医药卫生—内科学]