A Computational Model of Inhibition of HIV-1 by Interferon-Alpha
A Computational Model of Inhibition of HIV-1 by Interferon-Alpha
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DOI：
10.1371/journal.pone.0152316
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发表时间：
2016-03-24
期刊：
影响因子：
3.7
通讯作者：
Rudin, Cynthia
中科院分区：
文献类型：
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作者：
Browne, Edward P.;Letham, Benjamin;Rudin, Cynthia
1型干扰素如干扰素- α (IFN α)通过上调干扰病毒生命周期中特定步骤的基因表达来抑制人类免疫缺陷病毒（HIV-1）的复制。因此，这一途径代表了基于免疫疗法的潜在靶标，可以改变宿主-病毒相互作用的动态，使宿主受益。为了更深入地了解IFN α如何影响HIV-1感染的传播机制，我们将HIV-1与CD4 T细胞和IFN α的相互作用建模为一个动态系统。然后，使用来自传播HIV-1感染的细胞培养模型的实验数据对该模型进行测试。我们发现，IFN α诱导阻断HIV-1感染早期和晚期的可逆细胞状态的模型，结合向这些状态转化的饱和率，能够成功地拟合实验数据集。敏感性分析表明，IFN α的抑制效力特别依赖于特定的网络参数和速率常数。该模型将有助于设计针对hiv -1感染个体的IFN α网络的新疗法，并可能作为理解IFNa与其他病毒相互作用的模板。
Type 1 interferons such as interferon-alpha (IFN alpha) inhibit replication of Human immunodeficiency virus (HIV-1) by upregulating the expression of genes that interfere with specific steps in the viral life cycle. This pathway thus represents a potential target for immune based therapies that can alter the dynamics of host-virus interactions to benefit the host. To obtain a deeper mechanistic understanding of how IFN alpha impacts spreading HIV-1 infection, we modeled the interaction of HIV-1 with CD4 T cells and IFN alpha as a dynamical system. This model was then tested using experimental data from a cell culture model of spreading HIV-1 infection. We found that a model in which IFN alpha induces reversible cellular states that block both early and late stages of HIV-1 infection, combined with a saturating rate of conversion to these states, was able to successfully fit the experimental dataset. Sensitivity analysis showed that the potency of inhibition by IFN alpha was particularly dependent on specific network parameters and rate constants. This model will be useful for designing new therapies targeting the IFN alpha network in HIV-1-infected individuals, as well as potentially serving as a template for understanding the interaction of IFNa with other viruses.