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
Kirchhoff F
中科院分区:
医学1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

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大多数猿免疫缺陷病毒使用它们的Nef蛋白来拮抗宿主限制因子tetherin。人类tetherin的缺失赋予Nef抗性,代表了成功的人畜共患病传播的障碍。HIV-1 M组进化为利用病毒蛋白U(Vpu)来抵消栓蛋白。尽管HIV-1 O组在人类中传播迅速,但它还没有进化出基于Vpu的Tetherin拮抗作用。在这里,我们发现HIV-1 O组Nef靶向与该缺失相邻的区域,以抑制人栓蛋白转运到细胞表面,增强病毒体释放,并增加病毒对干扰素-α抑制的抗性。O组病毒的推断的共同祖先的Nef蛋白也对人栓蛋白有活性。因此,Nef介导的人类tetherin的拮抗作用在HIV-1 O组传播之前就已经形成,并可能促进了二次病毒传播。我们的结果可以解释O群HIV-1的流行。
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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