Low level viral persistence after infection with LCMV: a quantitative insight through numerical bifurcation analysis
Low level viral persistence after infection with LCMV: a quantitative insight through numerical bifurcation analysis
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DOI：
10.1016/s0025-5564(01)00072-4
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发表时间：
2001-09-01
影响因子：
4.3
通讯作者：
Bocharov, G
中科院分区：
文献类型：
--
作者：
Luzyanina, T;Engelborghs, K;Bocharov, G
许多重要的病毒在宿主免疫力面前以非常低的水平在体内持续存在，并且可能影响这种“感染免疫力”状态的维持。为了定量分析低水平病毒持续性，我们使用了对淋巴细胞性脉络丛脑膜炎病毒（LCMV）的抗病毒细胞毒性T淋巴细胞（CTL）反应的数学模型。这个模型，描述了一个非线性系统的延迟微分方程（DDE），研究使用数值分岔分析技术的DDE。域低水平LCMV与CTL内存共存是可能的，无论是作为一个平衡状态或振荡模式，被确定在空间的模型参数表征病毒和CTL群体之间的相互作用。我们的分析表明，低于常规检测限（约100 pfu/脾）的复制能力的病毒在免疫宿主中的共存作为一种平衡状态，需要每天的相对增长率的病毒种群减少至少5倍相比，感染的急性期。振荡模式的动态持续LCMV和CTL的记忆，与病毒种群之间变化1和100 pfu每个脾脏，是可能的，在相当窄的间隔内的病毒生长率和前体CTL种群死亡。尽管病毒复制率似乎决定了低水平病毒持久性的稳定性，但它不影响病毒群体的稳态水平，除了非常低的值。(C)2001年由Elsevier Science Inc.出版
Many important viruses persist at very low levels in the body in the face of host immunity, and may influence the maintenance of this state of 'infection immunity'. To analyse low level viral persistence in quantitative terms, we use a mathematical model of antiviral cytotoxic T lymphocyte (CTL) response to lymphocytic choriomeningitis virus (LCMV). This model, described by a non-linear system of delay differential equations (DDEs), is studied using numerical bifurcation analysis techniques for DDEs. Domains where low level LCMV coexistence with CTL memory is possible, either as an equilibrium state or an oscillatory pattern, are identified in spaces of the model parameters characterising the interaction between virus and CTL populations. Our analysis suggests that the coexistence of replication competent virus below the conventional detection limit (of about 100 pfu per spleen) in the immune host as an equilibrium state requires the per day relative growth rate of the virus population to decrease at least 5-fold compared to the acute phase of infection. Oscillatory patterns in the dynamics of persisting LCMV and CTL memory, with virus population varying between 1 and 100 pfu per spleen, are possible within quite narrow intervals of the rates of virus growth and precursor CTL population death. Whereas the virus replication rate appears to determine the stability of the low level virus persistence, it does not affect the steady-state level of the viral population, except for very low values. (C) 2001 Published by Elsevier Science Inc.