Modeling amantadine treatment of influenza A virus in vitro.
Modeling amantadine treatment of influenza A virus in vitro.
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DOI：
10.1016/j.jtbi.2008.05.031
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发表时间：
2008-09-21
影响因子：
2
通讯作者：
Perelson, Alan S.
中科院分区：
文献类型：
--
作者：
Beauchemin, Catherine A. A.;McSharry, James J.;Drusano, George L.;Nguyen, Jack T.;Went, Gregory T.;Ribeiro, Ruy M.;Perelson, Alan S.
我们分析了流感A/奥尔巴尼/1/98（H3 N2）病毒感染的动力学，使用一组数学模型突出体内和体外感染之间的差异。例如，我们发现，包括由于细胞进入而导致的病毒体损失对于体外模型是关键的，但对于体内模型不是。实验在体外在中空纤维（HF）系统内对流感病毒感染的MDCK细胞进行，该系统用于连续递送药物金刚烷胺。HF系统捕获流感感染的动态，并且是用于产生实验数据的受控环境，这些实验数据很好地适合于数学建模。从拟合我们的数学模型HF实验数据获得的参数估计是一致的，与先前获得的原发性感染的人类模型。我们发现，在37°C的正常实验条件下，流感A/奥尔巴尼/1/98（H3 N2）病毒粒子迅速失去感染性，半衰期为~ 6.6 ± 0.2小时，而有效感染的MDCK细胞的寿命为~ 13小时。最后，使用我们的模型，我们估计金刚烷胺在阻断病毒感染方面的最大功效为~ 74%，并表明这种低的最大功效可能是由于耐药性的快速发展。
We analyzed the dynamics of an influenza A/Albany/1/98 (H3N2) viral infection, using a set of mathematical models highlighting the differences between in vivo and in vitro infection. For example, we found that including virion loss due to cell entry was critical for the in vitro model but not for the in vivo model. Experiments were performed on influenza virus-infected MDCK cells in vitro inside a hollow-fiber (HF) system, which was used to continuously deliver the drug amantadine. The HF system captures the dynamics of an influenza infection, and is a controlled environment for producing experimental data which lend themselves well to mathematical modeling. The parameter estimates obtained from fitting our mathematical models to the HF experimental data are consistent with those obtained earlier for a primary infection in a human model. We found that influenza A/Albany/1/98 (H3N2) virions under normal experimental conditions at 37°C rapidly lose infectivity with a half-life of ~ 6.6 ± 0.2 h, and that the lifespan of productively infected MDCK cells is ~ 13 h. Finally, using our models we estimated that the maximum efficacy of amantadine in blocking viral infection is ~ 74%, and showed that this low maximum efficacy is likely due to the rapid development of drug resistance.
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影响因子：
168.9
作者：
Gubareva, LV;Kaiser, L;Hayden, FG
通讯作者：
Hayden, FG
影响因子：
4.9
作者：
BILELLO, JA;BAUER, G;DRUSANO, GL
通讯作者：
DRUSANO, GL
影响因子：
5.4
作者：
Huang, I-Chueh;Li, Wenhui;Farzan, Michael
通讯作者：
Farzan, Michael
影响因子：
6.4
作者：
Deyde, Varough M.;Xu, Xiyan;Klimov, Alexander I.
通讯作者：
Klimov, Alexander I.
影响因子：
7.6
作者：
Ilyushina, Natalia A.;Bovin, Nicolai V.;Govorkova, Elena A.
通讯作者：
Govorkova, Elena A.