1. Nef Proteins of Epidemic HIV-1 Group O Strains Antagonize Human Tetherin.
- Author
-
Kluge, Silvia F., Mack, Katharina, Iyer, Shilpa S., Pujol, François M., Heigele, Anke, Learn, Gerald H., Usmani, Shariq M., Sauter, Daniel, Joas, Simone, Hotter, Dominik, Bibollet-Ruche, Frederic, Plenderleith, Lindsey J., Peeters, Martine, Geyer, Matthias, Sharp, Paul M., Fackler, Oliver T., Hahn, Beatrice H., and Kirchhoff, Frank
- Abstract
Summary 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF