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

• Verfasst von: Kluge, Silvia Franziska [VerfasserIn]
• Verfasst von: Pujol, Franc̦ois [VerfasserIn]
• Verfasst von: Fackler, Oliver Till [VerfasserIn]
• Titel: Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin
• Verf.angabe: 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, and Frank Kirchhoff
• E-Jahr: 2014
• Jahr: 12 November 2014
• Umfang: 12 S.
• Fussnoten: Gesehen am 11.08.2020
• Titel Quelle: Enthalten in: Cell host and microbe
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 2007
• Jahr Quelle: 2014
• Band/Heft Quelle: 16(2014), 5, Seite 639-650
• ISSN Quelle: 1934-6069
• DOI: doi:10.1016/j.chom.2014.10.002
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1726745295

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-a. 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.