Pandemic HIV-1 Vpu overcomes intrinsic herd immunity mediated by tetherin

Shingo Iwami, Kei Sato, Satoru Morita, Hisashi Inaba, Tomoko Kobayashi, Junko S. Takeuchi, Yuichi Kimura, Naoko Misawa, Fengrong Ren, Yoh Iwasa, Kazuyuki Aihara, Yoshio Koyanagi

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9 Citations (Scopus)


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.

Original languageEnglish
Article number12256
JournalScientific reports
Publication statusPublished - Jul 17 2015

All Science Journal Classification (ASJC) codes

  • General


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