title: Quantifying the effect of Vpu on the promotion of HIV-1 replication in the humanized mouse model.
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.
authors.affiliation: Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, Fukuoka, 812-8581, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakaoka
authors.affiliation: Theoretical Biology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Boer
authors.affiliation: Department of Mathematical and Systems Engineering, Shizuoka University, Shizuoka, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Morita
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, 53 Shogoinkawara-cho, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Misawa
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, 53 Shogoinkawara-cho, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
authors.affiliation: Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.|Graduate School of Information Science and Technology, The University of Tokyo, Tokyo, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Aihara
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, 53 Shogoinkawara-cho, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan. ksato@virus.kyoto-u.ac.jp.|CREST, JST, Saitama, Japan. ksato@virus.kyoto-u.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, Fukuoka, 812-8581, Japan. siwami@kyushu-u.org.|CREST, JST, Saitama, Japan. siwami@kyushu-u.org.|PRESTO, JST, Saitama, Japan. siwami@kyushu-u.org.
authors.forename: Shingo
authors.initials: S
authors.lastname: Iwami
mesh_terms: D000818:Animals; D015497:HIV-1 / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008962:Models, Theoretical; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D014779:Virus Replication; D000086082:Viroporin Proteins
chemical_list: D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
keywords: HIV-1; Humanized mouse model; Mathematical model; Tetherin; Virus dynamics; Vpu