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dc.contributor.authorIkeda, Hiroki
dc.contributor.authorNakaoka, Shinji
dc.contributor.authorde Boer, Rob J.
dc.contributor.authorMorita, Satoru
dc.contributor.authorMisawa, Naoko
dc.contributor.authorKoyanagi, Yoshio
dc.contributor.authorAihara, Kazuyuki
dc.contributor.authorSato, Kei
dc.contributor.authorIwami, Shingo
dc.contributor.alternative三沢, 尚子
dc.contributor.alternative小柳, 義夫
dc.contributor.alternative佐藤, 佳
dc.date.accessioned2017-10-16T02:17:06Z-
dc.date.available2017-10-16T02:17:06Z-
dc.date.issued2016-04-28
dc.identifier.issn1742-4690
dc.identifier.urihttp://hdl.handle.net/2433/227518-
dc.description.abstract[Background]Tetherin is an intrinsic anti-viral factor impairing the release of nascent HIV-1 particles from infected cells. Vpu, an HIV-1 accessory protein, antagonizes the anti-viral action of tetherin. Although previous studies using in vitro cell culture systems have revealed the molecular mechanisms of the anti-viral action of tetherin and the antagonizing action of Vpu against tetherin, it still remains unclear how Vpu affects the kinetics of HIV-1 replication in vivo. [Results]To quantitatively assess the role of Vpu in viral replication in vivo, we analyzed time courses of experimental data with viral load and target cell levels in the peripheral blood of humanized mice infected with wild-type and vpu-deficient HIV-1. Our recently developed mathematical model describes the acute phase of this infection reasonably, and allowed us to estimate several parameters characterizing HIV-1 infection in mice. Using a technique of Bayesian parameter estimation, we estimate distributions of the basic reproduction number of wild-type and vpu-deficient HIV-1. This reveals that Vpu markedly increases the rate of viral replication in vivo. [Conclusions]Combining experiments with mathematical modeling, we provide an estimate for the contribution of Vpu to viral replication in humanized mice.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherSpringer Nature
dc.rights© 2016 Ikeda et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
dc.subjectVirus dynamics
dc.subjectMathematical model
dc.subjectVpu
dc.subjectTetherin
dc.subjectHIV-1
dc.subjectHumanized mouse model
dc.titleQuantifying the effect of Vpu on the promotion of HIV-1 replication in the humanized mouse model
dc.type.niitypeJournal Article
dc.identifier.jtitleRetrovirology
dc.identifier.volume13
dc.relation.doi10.1186/s12977-016-0252-2
dc.textversionpublisher
dc.identifier.artnum23
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