Bailey J J, Fletcher J E, Chuck E T, Shrager R I
Laboratory of Applied Studies, National Institutes of Health, Bethesda, Maryland 20892.
Biosystems. 1992;26(3):177-83. doi: 10.1016/0303-2647(92)90077-c.
This report describes a kinetic model of in vitro cytopathology involving interactions of human immunodeficiency virus (HIV) with CD4+ helper T lymphocytes. The model uses nonlinearly coupled, ordinary differential equations to simulate the dynamics of infected and uninfected cells and free virions. It is assumed that resting cells are more readily infected than activated cells, but once infected, only activated cells produce more virus. Resting cells can be activated by some appropriate stimulus (e.g. phytohemagglutinin, soluble antigen). The model predicts that the initial inoculum of virus is taken up by resting cells and without stimulation the system comes to a steady state of two populations, namely infected and uninfected cells. Stimulation of this system produces two additional populations, namely infected and uninfected activated cells which, along with the previous populations, exhibit cyclic behavior of growth, viral expression/release, and death. Additional stimuli enhance or diminish the cyclic behavior depending upon their occurrence in time. These simulations suggest a similar dynamics in human HIV infection and may explain a major factor responsible for the widely varying depletion rate of (CD4+) helper T cells in AIDS patients.
本报告描述了一种体外细胞病理学动力学模型，该模型涉及人类免疫缺陷病毒（HIV）与CD4 +辅助性T淋巴细胞的相互作用。该模型使用非线性耦合的常微分方程来模拟受感染细胞、未受感染细胞和游离病毒粒子的动态变化。假定静息细胞比活化细胞更容易被感染，但一旦被感染，只有活化细胞会产生更多病毒。静息细胞可被某些适当的刺激（如植物血凝素、可溶性抗原）激活。该模型预测，病毒的初始接种物会被静息细胞摄取，并且在没有刺激的情况下，系统会达到两种细胞群体（即受感染细胞和未受感染细胞）的稳定状态。对该系统的刺激会产生另外两种细胞群体，即受感染的活化细胞和未受感染的活化细胞，它们与之前的细胞群体一起呈现出生长、病毒表达/释放和死亡的循环行为。额外的刺激会根据其发生时间增强或减弱这种循环行为。这些模拟结果表明人类HIV感染中存在类似的动态变化，并可能解释了导致艾滋病患者中（CD4 +）辅助性T细胞耗竭率差异很大的一个主要因素。
