Viral dynamics in vivo: Limitations on estimates of intracellular delay and virus decay
Viral dynamics in vivo: Limitations on estimates of intracellular delay and virus decay
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DOI：
10.1073/pnas.93.14.7247
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发表时间：
1996-07-09
影响因子：
11.1
通讯作者：
Nowak, MA
中科院分区：
文献类型：
--
作者：
Herz, AVM;Bonhoeffer, S;Nowak, MA
人类免疫缺陷病毒1型（HIV-1）和B肝炎病毒（HBV）感染的抗病毒药物治疗导致血浆病毒载量迅速降低。病毒下降发生在几个阶段，并提供有关体内病毒复制的重要动力学常数和药效学特性的信息。我们开发了一个数学模型，考虑到病毒生命周期的细胞内阶段，定义为感染细胞和产生新的病毒颗粒之间的时间。我们推导出的动力学与逆转录酶抑制剂，蛋白酶抑制剂，或两者的组合治疗后的解析解。对于HIV-I，我们的研究结果表明，血浆病毒的快速衰减阶段（第2-7天）允许精确估计生产性感染细胞的周转率。初始准稳定期（第0-1天）和过渡期（第1-2天）由药理学和细胞内延迟、游离病毒颗粒清除和感染细胞衰变的综合效应解释，仅根据病毒载量数据无法可靠估计前三个量;此类估计需要额外测量。与HIV-1相反，对于HBV，我们的模型预测，频繁的早期血浆病毒采样将导致对游离病毒半衰期和给药药物的药理学性质的可靠估计。另一方面，对于HBV，感染细胞的半衰期不能通过血浆病毒衰变来估计。
Anti-viral drug treatment of human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) infections causes rapid reduction in plasma virus load. Viral decline occurs in several phases and provides information on important kinetic constants of virus replication in vivo and pharmacodynamical properties. We develop a mathematical model that takes into account the intracellular phase of the viral life-cycle, defined as the time between infection of a cell and production of new virus particles. We derive analytic solutions for the dynamics following treatment with reverse transcriptase inhibitors, protease inhibitors, or a combination of both. For HIV-I, our results show that the phase of rapid decay in plasma virus (days 2-7) allows precise estimates for the turnover rate of productively infected cells. The initial quasi-stationary phase (days 0-1) and the transition phase (days 1-2) are explained by the combined effects of pharmacological and intracellular delays, the clearance of free virus particles, and the decay of infected cells, Reliable estimates of the first three quantities are not possible from data on virus load only; such estimates require additional measurements. In contrast with HIV-1, for HBV our model predicts that frequent early sampling of plasma virus will lead to reliable estimates of the free virus half-life and the pharmacological properties of the administered drug. On the other hand, for HBV the half-life of infected cells cannot be estimated from plasma virus decay.