TY - JOUR
T1 - Pandemic HIV-1 Vpu overcomes intrinsic herd immunity mediated by tetherin
AU - Iwami, Shingo
AU - Sato, Kei
AU - Morita, Satoru
AU - Inaba, Hisashi
AU - Kobayashi, Tomoko
AU - Takeuchi, Junko S.
AU - Kimura, Yuichi
AU - Misawa, Naoko
AU - Ren, Fengrong
AU - Iwasa, Yoh
AU - Aihara, Kazuyuki
AU - Koyanagi, Yoshio
N1 - Funding Information:
This work was supported in part by JST PRESTO program (to S.I.); JST CREST program (to S.I. and K.S.); a Grant-in-Aid for Young Scientists B25800092 (to S.I.) from the Japan Society for the Promotion of Science (JSPS); Inamori Foundation (to S.I.); the Aihara Innovative Mathematical Modeling Project, JSPS, through the “Funding Program for World-Leading Innovative R & D on Science and Technology (FIRST Program)”, initiated by Council for Science and Technology Policy (to S.I., K.A., and K.S.); Kyushu University Interdisciplinary Programs in Education and Projects in Research Development (to S.I.); Takeda Science Foundation (to K.S.); Sumitomo Foundation Research Grant (to K.S.); Senshin Medical Research Foundation (to K.S.); Imai Memorial Trust for AIDS Research (to K.S.); Ichiro Kanehara Foundation (to K.S.); Kanae Foundation for the Promotion of Medical Science (to K.S.); Suzuken Memorial Foundation (to K.S.).
PY - 2015/7/17
Y1 - 2015/7/17
N2 - 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.
AB - 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.
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U2 - 10.1038/srep12256
DO - 10.1038/srep12256
M3 - Article
C2 - 26184634
AN - SCOPUS:84937510281
SN - 2045-2322
VL - 5
JO - Scientific reports
JF - Scientific reports
M1 - 12256
ER -
