A Computational Model of Inhibition of HIV-1 by Interferon-Alpha

作者：Browne Edward P^*; Letham Benjamin; Rudin Cynthia

来源：PLos One, 2016, 11(3): e0152316.

DOI：10.1371/journal.pone.0152316

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.

• 出版日期2016-3-24
• 单位MIT