Lytic cycle: A defining process in oncolytic virotherapy
Lytic cycle: A defining process in oncolytic virotherapy
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裂解周期：溶瘤病毒疗法的决定性过程
DOI：
10.1016/j.apm.2012.12.004
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发表时间：
2013-04-15
影响因子：
5
通讯作者：
Wei, Junjie
中科院分区：
文献类型：
--
作者：
Wang, Yujie;Tian, Jianjun Paul;Wei, Junjie
病毒裂解周期是溶瘤病毒治疗中的重要过程。大多数溶瘤病毒疗法的数学模型不包括这个过程。在本文中，我们提出了一个数学模型的基础上，溶瘤病毒治疗的病毒溶解周期。病毒裂解周期由两个参数表征，即病毒裂解周期的时间段和病毒爆发大小。病毒裂解周期的时间段被建模为延迟参数。该模型是一个非线性时滞微分方程组。该模型揭示了一个显著的特点，即病毒裂解周期的临界值由病毒爆发的大小决定。突发大小有两个阈值。在第一个阈值以下，对于任意非负时滞，系统存在不稳定的平凡平衡点和全局稳定的无病毒平衡点，而当爆发规模大于第一个阈值时，系统存在第三个正平衡点.当爆发大小高于第二阈值时，病毒裂解周期的延迟参数的分叉值与爆发大小之间存在函数关系。当爆发规模大于第二阈值时，当病毒裂解周期小于分歧值时，系统的正平衡点是稳定的，而当裂解周期大于分歧值时，系统具有轨道稳定的周期解.然而，当突发规模变大时，该分叉值变小。病毒裂解周期可以解释在许多研究中观察到的振荡现象。一个重要的临床意义是，当一种病毒被修饰用于病毒治疗时，应根据其对裂解周期的影响来仔细地修改爆发大小，使得病毒裂解周期在能够打破正平衡或周期解的稳定性的适当范围内。(C)2012 Elsevier Inc. All rights reserved.
The viral lytic cycle is an important process in oncolytic virotherapy. Most mathematical models for oncolytic virotherapy do not incorporate this process. In this article, we propose a mathematical model with the viral lytic cycle based on the basic mathematical model for oncolytic virotherapy. The viral lytic cycle is characterized by two parameters, the time period of the viral lytic cycle and the viral burst size. The time period of the viral lytic cycle is modeled as a delay parameter. The model is a nonlinear system of delay differential equations. The model reveals a striking feature that the critical value of the period of the viral lytic cycle is determined by the viral burst size. There are two threshold values for the burst size. Below the first threshold, the system has an unstable trivial equilibrium and a globally stable virus free equilibrium for any nonnegative delay, while the system has a third positive equilibrium when the burst size is greater than the first threshold. When the burst size is above the second threshold, there is a functional relation between the bifurcation value of the delay parameter for the period of the viral lytic cycle and the burst size. If the burst size is greater than the second threshold, the positive equilibrium is stable when the period of the viral lytic cycle is smaller than the bifurcation value, while the system has orbitally stable periodic solutions when the period of the lytic cycle is longer than the bifurcation value. However, this bifurcation value becomes smaller when the burst size becomes bigger. The viral lytic cycle may explain the oscillation phenomena observed in many studies. An important clinic implication is that the burst size should be carefully modified according to its effect on the lytic cycle when a type of a virus is modified for virotherapy, so that the period of the viral lytic cycle is in a suitable range which can break away the stability of the positive equilibria or periodic solutions. (C) 2012 Elsevier Inc. All rights reserved.