Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin.
Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin.
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DOI:
10.1016/j.chom.2014.10.002
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发表时间:
2014-11-12
影响因子:
30.3
通讯作者:
Kirchhoff F
中科院分区:
文献类型:
--
作者:
Kluge SF;Mack K;Iyer SS;Pujol FM;Heigele A;Learn GH;Usmani SM;Sauter D;Joas S;Hotter D;Bibollet-Ruche F;Plenderleith LJ;Peeters M;Geyer M;Sharp PM;Fackler OT;Hahn BH;Kirchhoff F
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.
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