A Computational Model of Inhibition of HIV-1 by Interferon-Alpha
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Browne-2016-A Computational Mode.pdf
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1.88 MB
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Author(s)
Browne, Edward P.
Letham, Benjamin
Rudin, Cynthia
Date Issued
March 2016
Journal
PLOS ONE
Publisher
Public Library of Science
Citation
Browne, Edward P., Benjamin Letham, and Cynthia Rudin. “A Computational Model of Inhibition of HIV-1 by Interferon-Alpha.” Edited by Hans A Kestler. PLoS ONE 11, no. 3 (March 24, 2016): e0152316.
Version
Final published version
Abstract
Type 1 interferons such as interferon-alpha (IFNα) 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 IFNα impacts spreading HIV-1 infection, we modeled the interaction of HIV-1 with CD4 T cells and IFNα 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 IFNα 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 IFNα was particularly dependent on specific network parameters and rate constants. This model will be useful for designing new therapies targeting the IFNα network in HIV-1-infected individuals, as well as potentially serving as a template for understanding the interaction of IFNα with other viruses.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Operations Research Center
Sloan School of Management
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0152316
