Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin

Silvia F. Kluge, Katharina Mack, Shilpa S. Iyer, François M. Pujol, Anke Heigele, Gerald H. Learn, Shariq M. Usmani, Daniel Sauter, Simone Joas, Dominik Hotter, Frederic Bibollet-Ruche, Lindsey J. Plenderleith, Martine Peeters, Matthias Geyer, Paul M. Sharp, Oliver T. Fackler, Beatrice H. Hahn*, Frank Kirchhoff

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Most simian immunodeficiency viruses use their Nef protein to antagonize the host restriction factor tetherin. A deletion in human tetherin confers Nef resistance, representing a hurdle to successful zoonotic transmission. HIV-1 group M evolved to utilize the viral protein U (Vpu) to counteract tetherin. Although HIV-1 group O has spread epidemically in humans, it has not evolved a Vpu-based tetherin antagonism. Here we show that HIV-1 group O Nef targets a region adjacent to this deletion to inhibit transport of human tetherin to the cell surface, enhances virion release, and increases viral resistance to inhibition by interferon-α. The Nef protein of the inferred common ancestor of group O viruses is also active against human tetherin. Thus, Nef-mediated antagonism of human tetherin evolved prior to the spread of HIV-1 group O and likely facilitated secondary virus transmission. Our results may explain the epidemic spread of HIV-1 group O.

Original languageEnglish
Pages (from-to)639-650
Number of pages12
JournalCell Host & Microbe
Issue number5
Publication statusPublished - 12 Nov 2014


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