Modeling the intracellular dynamics for Vif-APO mediated HIV-1 virus infection
Wang Yi1,2; Lai LuHua1,3
AbstractThe 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.
KeywordBiochemical Network Modeling Host-virus Interaction Hiv-1 Virus Vif Apo Gag Tat
Indexed BySCI
WOS IDWOS:000280808100003
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Cited Times:4[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Corresponding AuthorLai LuHua
Affiliation1.Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China
2.Peking Univ, Sch Phys, Beijing 100871, Peoples R China
3.Peking Univ, BNLMS, State Key Lab Struct Chem Unstable & Stable Speci, Coll Chem & Mol Engn, Beijing 100871, Peoples R China
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Wang Yi,Lai LuHua. Modeling the intracellular dynamics for Vif-APO mediated HIV-1 virus infection[J]. CHINESE SCIENCE BULLETIN,2010,55(22):2329-2340.
APA Wang Yi,&Lai LuHua.(2010).Modeling the intracellular dynamics for Vif-APO mediated HIV-1 virus infection.CHINESE SCIENCE BULLETIN,55(22),2329-2340.
MLA Wang Yi,et al."Modeling the intracellular dynamics for Vif-APO mediated HIV-1 virus infection".CHINESE SCIENCE BULLETIN 55.22(2010):2329-2340.
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