Modeling plasma virus concentration during primary HIV infection
Modeling plasma virus concentration during primary HIV infection
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DOI：
10.1006/jtbi.2000.1076
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发表时间：
2000-04-07
影响因子：
2
通讯作者：
Perelson, AS
中科院分区：
文献类型：
--
作者：
Stafford, MA;Corey, L;Perelson, AS
在原发性HIV感染期间，血浆中的病毒载量增加，达到峰值，然后下降。菲利普斯认为这种下降是由于对HIV感染敏感的细胞数量有限，而其他作者则认为病毒血症的下降是由于免疫反应。在这里，我们解决这个问题，通过开发模型的主要HIV-1感染，并通过比较这些模型的预测与数据从10个抗逆转录病毒，药物初治，感染患者。应用非线性最小二乘估计，我们发现，相对较小的参数变化能够模仿患者病毒载量数据中发现的高度多样化的模式。这种方法产生了在初次感染期间生产性感染细胞的平均寿命的估计值为2.5天，该值与通过药物扰动实验获得的结果一致。我们发现，从最初感染到病毒血症高峰后不久，所有十名患者的数据都与靶细胞限制模型一致。然而，一些患者中病毒浓度随后下降和恢复的动力学与靶细胞限制模型的预测不一致。我们说明，两种可能的免疫反应机制，细胞毒性T淋巴细胞破坏感染的靶细胞和细胞因子抑制病毒复制，可以解释病毒载量数据的下降，而不是由原来的靶细胞有限的模型预测。我们的结论是，一些额外的过程，可能是由CD 8 + T细胞介导的，是重要的，至少在一些患者。(C)北京大学出版社.
During primary HIV infection the viral load in plasma increases, reaches a peak, and then declines. Phillips has suggested that the decline is due to a limitation in the number of cells susceptible to HIV infection, while other authors have suggested that the decline in viremia is due to an immune response. Here we address this issue by developing models of primary HIV-1 infection, and by comparing predictions from these models with data from ten anti-retroviral, drug-naive, infected patients. Applying nonlinear least-squares estimation, we find that relatively small variations in parameters are capable of mimicking the highly diverse patterns found in patient viral load data. This approach yields an estimate of 2.5 days for the average lifespan of productively infected cells during primary infection, a Value that is consistent with results obtained by drug perturbation experiments. We find that the data from all ten patients are consistent with a target-cell-limited model from the time of initial infection until shortly after the peak in viremia. However, the kinetics of the subsequent fall and recovery in virus concentration in some patients are not consistent with the predictions of the target-cell-limited model. We illustrate that two possible immune response mechanisms, cytotoxic T lymphocyte destruction of infected target cells and cytokine suppression of viral replication, could account for declines in viral load data not predicted by the original target-cell-limited model. We conclude that some additional process, perhaps mediated by CD8 + T cells, is important in at least some patients. (C) 2000 Academic Press.