| Literature DB >> 25525794 |
Silvia F Kluge1, Katharina Mack1, Shilpa S Iyer2, François M Pujol3, Anke Heigele1, Gerald H Learn2, Shariq M Usmani1, Daniel Sauter1, Simone Joas1, Dominik Hotter1, Frederic Bibollet-Ruche2, Lindsey J Plenderleith4, Martine Peeters5, Matthias Geyer6, Paul M Sharp4, Oliver T Fackler3, Beatrice H Hahn7, Frank Kirchhoff8.
Abstract
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.Entities:
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Year: 2014 PMID： 25525794 PMCID： PMC4274627 DOI： 10.1016/j.chom.2014.10.002
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023