DYNAMICS OF HIV-INFECTION OF CD4+ T-CELLS
DYNAMICS OF HIV-INFECTION OF CD4+ T-CELLS
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DOI：
10.1016/0025-5564(93)90043-a
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发表时间：
1993-03-01
影响因子：
4.3
通讯作者：
DEBOER, R
中科院分区：
文献类型：
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作者：
PERELSON, AS;KIRSCHNER, DE;DEBOER, R
我们研究了HIV与CD4+ T细胞相互作用的模型，该模型考虑了四个群体：未感染的T细胞，潜伏感染的T细胞，活跃感染的T细胞和游离病毒。使用这个模型，我们表明，许多令人困惑的HIV感染的数量特征可以简单地解释。我们还考虑了AZT对病毒生长和T细胞种群动力学的影响，模型表现出两个定态，一个是无病毒的未感染状态，另一个是有病毒和感染的T细胞的地方感染状态。我们表明，如果N，每活跃感染的T细胞产生的感染性病毒体的数量，是小于一个临界值，N（临界），那么未感染状态是唯一的稳定状态，在非负的orthant，这种状态是稳定的。对于N > N（临界），未感染状态是不稳定的，而地方性感染状态可以是稳定的，也可以是不稳定的，并被稳定的极限环包围。使用数值分岔技术，我们映射出这些不同的行为的参数制度。振荡行为似乎位于生物现实参数值的区域之外。当地方性感染状态稳定时，其特征在于与未感染状态相比T细胞数量减少。因此，T细胞消耗通过建立新的稳态而发生。建立这个新的稳态的动力学研究数值和通过准稳态近似。我们开发的动力学在早期的时候，其中游离病毒迅速结合到T细胞，在中间的时间尺度，其中病毒呈指数级增长，和第三个时间尺度上，病毒生长放缓，地方性感染的稳态接近的近似。利用准稳态近似，该模型可以简化为两个常微分方程，总结了大部分的动力学行为。我们计算了地方性感染状态下T细胞的水平，并展示了该水平如何随模型中的参数而变化。该模型预测，不同的病毒株，其特征在于在感染的T细胞内产生不同数量的感染性病毒体，可以引起不同量的T细胞消耗和产生消耗在不同rate.Two版本的模型进行了研究。在一种情况下，来自前体的T细胞来源是恒定的，而在另一种情况下，T细胞来源随着病毒载量而减少，模拟了T细胞前体的感染和杀伤。后者比具有恒定源的模型给出更现实的预测。
We examine a model for the interaction of HIV with CD4+ T cells that considers four populations: uninfected T cells, latently infected T cells, actively infected T cells, and free virus. Using this model we show that many of the puzzling quantitative features of HIV infection can be explained simply. We also consider effects of AZT on viral growth and T-cell population dynamics.The model exhibits two steady states, an uninfected state in which no virus is present and an endemically infected state, in which virus and infected T cells are present. We show that if N, the number of infectious virions produced per actively infected T cell, is less a critical value, N(crit), then the uninfected state is the only steady state in the nonnegative orthant, and this state is stable. For N > N(crit), the uninfected state is unstable, and the endemically infected state can be either stable, or unstable and surrounded by a stable limit cycle. Using numerical bifurcation techniques we map out the parameter regimes of these various behaviors. Oscillatory behavior seems to lie outside the region of biologically realistic parameter values. When the endemically infected state is stable, it is characterized by a reduced number of T cells compared with the uninfected state. Thus T-cell depletion occurs through the establishment of a new steady state. The dynamics of the establishment of this new steady state are examined both numerically and via the quasi-steady-state approximation. We develop approximations for the dynamics at early times in which the free virus rapidly binds to T cells, during an intermediate time scale in which the virus grows exponentially, and a third time scale on which viral growth slows and the endemically infected steady state is approached. Using the quasi-steady-state approximation the model can be simplified to two ordinary differential equations the summarize much of the dynamical behavior. We compute the level of T cells in the endemically infected state and show how that level varies with the parameters in the model. The model predicts that different viral strains, characterized by generating differing numbers of infective virions within infected T cells, can cause different amounts of T-cell depletion and generate depletion at different rates.Two versions of the model are studied. In one the source of T cells from precursors is constant, whereas in the other the source of T cells decreases with viral load, mimicking the infection and killing of T-cell precursors. The latter gives more realistic predictions than the model with a constant source.