A computational model of inhibition of HIV-1 by interferon-alpha
Public Deposited- Creator
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Browne, E.P.
- Affiliation: HIV Cure Center
- Other Affiliation: Massachusetts Institute of Technology
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Letham, B.
- Other Affiliation: Massachusetts Institute of Technology
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Rudin, C.
- Other Affiliation: Massachusetts Institute of Technology
- 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 immunebased 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.
- Date of publication
- 2016
- Keyword
- human
- virus inhibition
- drug response
- virus identification
- process development
- antiviral activity
- drug efficacy
- virus cell interaction
- nonhuman
- controlled study
- alpha interferon
- CD4+ T lymphocyte
- growth inhibition
- antivirus agent
- Human immunodeficiency virus 1
- mathematical computing
- mathematical model
- molecular dynamics
- drug potency
- sensitivity analysis
- DOI
- Identifier
- https://dx.doi.org/10.1371/journal.pone.0152316
- PMID 27010978
- Resource type
- Article
- Rights statement
- In Copyright
- License
- Attribution 3.0 United States
- Journal title
- PLoS ONE
- Journal volume
- 11
- Journal issue
- 3
- Language
- English
- ISSN
- 1932-6203
- Publisher
- Public Library of Science
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