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dc.contributor.authorBrowne, Edward P.
dc.contributor.authorLetham, Benjamin
dc.contributor.authorRudin, Cynthia
dc.date.accessioned2016-07-14T14:28:54Z
dc.date.available2016-07-14T14:28:54Z
dc.date.issued2016-03
dc.date.submitted2015-10
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1721.1/103599
dc.description.abstractType 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.en_US
dc.description.sponsorshipUnited States. Army Research Office (W911NF-15- 1-0155)en_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pone.0152316en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourcePublic Library of Scienceen_US
dc.titleA Computational Model of Inhibition of HIV-1 by Interferon-Alphaen_US
dc.typeArticleen_US
dc.identifier.citationBrowne, 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.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratoryen_US
dc.contributor.departmentMassachusetts Institute of Technology. Operations Research Centeren_US
dc.contributor.departmentSloan School of Managementen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorBrowne, Edward P.en_US
dc.contributor.mitauthorLetham, Benjaminen_US
dc.contributor.mitauthorRudin, Cynthiaen_US
dc.relation.journalPLOS ONEen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsBrowne, Edward P.; Letham, Benjamin; Rudin, Cynthiaen_US
dspace.embargo.termsNen_US
mit.licenseOPEN_ACCESS_POLICYen_US


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