Influence of follicular dendritic cells on decay of HIV during antiretroviral therapy
Influence of follicular dendritic cells on decay of HIV during antiretroviral therapy
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DOI：
10.1073/pnas.190065897
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发表时间：
2000-09-26
影响因子：
11.1
通讯作者：
Perelson, AS
中科院分区：
文献类型：
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作者：
Hlavacek, WS;Stilianakis, NI;Perelson, AS
HIV 1 型 (HIV-1) 感染的药物治疗会导致血浆病毒在初始阶段快速衰减，然后进入较慢的第二阶段衰减。为了研究保留在滤泡树突状细胞 (FDC) 上的 HIV-1 在此过程中的作用，我们开发并分析了包含 FDC 的淋巴组织 (LT) 中 HIV-1 动力学的数学模型。使用该模型对临床数据的分析表明，治疗期间 HIV-1 的衰减可能受到 FDC 相关病毒释放的影响。病毒衰变的双相特征可以通过 HIV-1 与 FDC 上受体的可逆多价结合来解释，这表明衰变的第二阶段不一定是由长寿或潜伏感染细胞引起的。此外。病毒清除和短命有效感染细胞的死亡可能比之前估计的要快。该模型具有合理的参数值，与血浆中病毒 RNA、FDC 上病毒 RNA、LT 中有效感染细胞的动力学测量结果一致。治疗期间 LT 中的 CD4(+) T 细胞。
Drug treatment of HIV type 1 (HIV-1) infection leads to a rapid initial decay of plasma virus followed by a slower second phase of decay. To investigate the role of HIV-1 retained on follicular dendritic cells (FDCs) in this process, we have developed and analyzed a mathematical model for HIV-1 dynamics in lymphoid tissue (LT) that includes FDCs. Analysis of clinical data using this model indicates that decay of HIV-1 during therapy may be influenced by release of FDC-associated virus. The biphasic character of viral decay can be explained by reversible multivalent binding of HIV-1 to receptors on FDCs, indicating that the second phase of decay is not necessarily caused by long-lived or latently infected cells. Furthermore. viral clearance and death of short-lived productively infected cells may be faster than previously estimated. The model, with reasonable parameter values, is consistent with kinetic measurements of viral RNA in plasma, viral RNA on FDCs, productively infected cells in LT. and CD4(+) T cells in LT during therapy.