Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo

Eri Yamada, Shinji Nakaoka, Lukas Klein, Elisabeth Reith, Simon Langer, Kristina Hopfensperger, Shingo Iwami, Gideon Schreiber, Frank Kirchhoff, Yoshio Koyanagi, Daniel Sauter, Kei Sato

研究成果: ジャーナルへの寄稿記事

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The HIV-1-encoded accessory protein Vpu exerts several immunomodulatory functions, including counteraction of the host restriction factor tetherin, downmodulation of CD4, and inhibition of NF-κB activity to facilitate HIV-1 infection. However, the relative contribution of individual Vpu functions to HIV-1 infection in vivo remained unclear. Here, we used a humanized mouse model and HIV-1 strains with selective mutations in vpu to demonstrate that the anti-tetherin activity of Vpu is a prerequisite for efficient viral spread during the early phase of infection. Mathematical modeling and gain-of-function mutations in SIVcpz, the simian precursor of pandemic HIV-1, corroborate this finding. Blockage of interferon signaling combined with transcriptome analyses revealed that basal tetherin levels are sufficient to control viral replication. These results establish tetherin as a key effector of the intrinsic immune defense against HIV-1, and they demonstrate that Vpu-mediated tetherin antagonism is critical for efficient viral spread during the initial phase of HIV-1 replication. The HIV-1-encoded accessory protein Vpu exerts several functions. Using a humanized mouse model and HIV-1 Vpu mutant viruses, Yamada et al. demonstrate that Vpu-mediated antagonism of the interferon-induced antiviral protein tetherin is critical for efficient viral spread during the initial phase of HIV-1 replication in vivo.

元の言語英語
ページ(範囲)110-120.e7
ジャーナルCell Host and Microbe
23
発行部数1
DOI
出版物ステータス出版済み - 1 10 2018

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

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    Yamada, E., Nakaoka, S., Klein, L., Reith, E., Langer, S., Hopfensperger, K., Iwami, S., Schreiber, G., Kirchhoff, F., Koyanagi, Y., Sauter, D., & Sato, K. (2018). Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo. Cell Host and Microbe, 23(1), 110-120.e7. https://doi.org/10.1016/j.chom.2017.12.009