Reassessing the Human Immunodeficiency Virus Type 1 Life Cycle through Age-Structured Modeling: Life Span of Infected Cells, Viral Generation Time, and Basic Reproductive Number, R0
Reassessing the Human Immunodeficiency Virus Type 1 Life Cycle through Age-Structured Modeling: Life Span of Infected Cells, Viral Generation Time, and Basic Reproductive Number, R0
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DOI：
10.1128/jvi.01799-08
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发表时间：
2009-08-01
影响因子：
5.4
通讯作者：
De Boer, Rob J.
中科院分区：
文献类型：
--
作者：
Althaus, Christian L.;De Vos, Anneke S.;De Boer, Rob J.
人类免疫缺陷病毒1型(HIV-1)感染者在药物治疗后病毒载量的快速下降被证明是由于感染细胞的高周转率而导致的快速损失，其世代时间约为1-2天。传统上，药物治疗后的病毒衰变动力学是用微分方程组模型来研究的，在该模型中，感染细胞的死亡率和病毒产生率都是恒定的。在这里，我们描述了病毒衰变动力学的年龄结构模型，其中病毒产生率和死亡率取决于感染细胞的年龄。为了调查年龄依赖率的影响，我们将这些模型与早期对病毒载量下降的描述进行了比较，并将它们与先前发表的数据进行了匹配。我们没有发现支持感染细胞死亡率增加的证据，但不能排除病毒产生率随着细胞年龄的增加而增加的可能性。特别是，我们证明了病毒产量随着感染细胞年龄的指数增加与数据完全一致。由于病毒产量的指数增长可以弥补感染细胞的指数损失，因此HIV-1感染细胞的死亡率可能高于之前的预期。我们讨论了这些发现对感染细胞的寿命、病毒世代时间和基本繁殖数R-0的影响。
The rapid decay of the viral load after drug treatment in patients infected with human immunodeficiency virus type 1 (HIV-1) has been shown to result from the rapid loss of infected cells due to their high turnover, with a generation time of around 1 to 2 days. Traditionally, viral decay dynamics after drug treatment is investigated using models of differential equations in which both the death rate of infected cells and the viral production rate are assumed to be constant. Here, we describe age-structured models of the viral decay dynamics in which viral production rates and death rates depend on the age of the infected cells. In order to investigate the effects of age-dependent rates, we compared these models with earlier descriptions of the viral load decay and fitted them to previously published data. We have found no supporting evidence that infected-cell death rates increase, but cannot reject the possibility that viral production rates increase, with the age of the cells. In particular, we demonstrate that an exponential increase in viral production with infected-cell age is perfectly consistent with the data. Since an exponential increase in virus production can compensate for the exponential loss of infected cells, the death rates of HIV-1-infected cells may be higher than previously anticipated. We discuss the implications of these findings for the life span of infected cells, the viral generation time, and the basic reproductive number, R-0.