Hlavacek W S, Stilianakis N I, Notermans D W, Danner S A, Perelson A S
Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10966-71. doi: 10.1073/pnas.190065897.
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.
1型人类免疫缺陷病毒（HIV-1）感染的药物治疗会导致血浆病毒迅速出现初始衰减，随后进入较慢的第二阶段衰减。为了研究滤泡树突状细胞（FDC）上保留的HIV-1在此过程中的作用，我们建立并分析了一个包含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进行分析表明，治疗期间HIV-1的衰减可能受FDC相关病毒释放的影响。病毒衰减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，这表明衰减的第二阶段不一定是由长寿命或潜伏感染细胞引起的。此外，短期有 productive感染细胞的病毒清除和死亡可能比先前估计的更快。该模型具有合理的参数值，与治疗期间血浆中病毒RNA、FDC上病毒RNA、LT中有 productive感染细胞以及LT中CD4(+) T细胞的动力学测量结果一致。
