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Title: Pandemic HIV-1 Vpu overcomes intrinsic herd immunity mediated by tetherin
Authors: Iwami, Shingo
Sato, Kei
Morita, Satoru
Inaba, Hisashi
Kobayashi, Tomoko
Takeuchi, Junko S.
Kimura, Yuichi
Misawa, Naoko
Ren, Fengrong
Iwasa, Yoh
Aihara, Kazuyuki
Koyanagi, Yoshio  kyouindb  KAKEN_id
Author's alias: 佐藤, 佳
小柳, 義夫
Issue Date: 17-Jul-2015
Publisher: Nature Publishing Group
Journal title: Scientific Reports
Volume: 5
Thesis number: 12256
Abstract: Among the four groups of HIV-1 (M ,N, O, and P), HIV-1M alone is pandemic and has rapidly expanded across the world. However, why HIV-1M has caused a devastating pandemic while the other groups remain contained is unclear. Interestingly, only HIV-1M Vpu, a viral protein, can robustly counteract human tetherin, which tethers budding virions. Therefore, we hypothesize that this property of HIV-1M Vpu facilitates human-to-human viral transmission. Adopting a multilayered experimental-mathematical approach, we demonstrate that HIV-1M Vpu confers a 2.38-fold increase in the prevalence of HIV-1 transmission. When Vpu activity is lost, protected human populations emerge (i.e., intrinsic herd immunity develops) through the anti-viral effect of tetherin. We also reveal that all Vpus of transmitted/founder HIV-1M viruses maintain anti-tetherin activity. These findings indicate that tetherin plays the role of a host restriction factor, providing 'intrinsic herd immunity', whereas Vpu has evolved in HIV-1M as a tetherin antagonist.
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
DOI(Published Version): 10.1038/srep12256
PubMed ID: 26184634
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